Case#: 1. Patient II-4 43 years

DiseaseAssertion: Hypertrophic cardiomyopathy and left ventricular noncompaction

FamilyInfo: Several family members have heart disease. One relative died from cardiac arrest at age 50.

ParentalTesting: NR

CasePresentingHPOs: NR

CaseHPOFreeText: The patient had thickened heart muscle, abnormal heartbeats, and extra ridges and deep spaces in the heart muscle.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

CasePreviousTesting: ECG, heart monitoring, heart ultrasound, and genetic testing

Genotyping Method: Next- generation sequencing and sanger sequencing

FunctionalAnalysis: computer testing suggested the ACTC1 gene change could weaken the protein

Variant: NM_005159.4:c.62C>T

Clinvar: 410264

CAID: CA16614451

gnomAD: NR

AdditionalInfo: His heart pumping ability was 55%. This article reported changes in his heart muscle cells.

Case#: 2 Patient II-5 46 years old

DiseaseAssertion: HCM and LVNC

FamilyInfo: Several family members have heart disease. One relative died from cardiac arrest at age 50.

ParentalTesting: NR

CasePresentingHPOs: NR

CaseHPOFreeText: The patient had thickened and enlarged heart muscle, abnormal heartbeats, and deep spaces in his heart muscle. He als had temporary episodes of reduced blood flow to the brain.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

CasePreviousTesting: ECG, heart monitoring, heart ultrasound, heart MRI, heart biopsy and genetic testing

Genotyping Method: NGS and sanger sequencing

FunctionalAnalysis:computer testing suggested the ACTC1 gene change could weaken the protein.

Variant: NM_005159.4:c.62C>T

Clinvar: 410264

CAID: CA16614451

gnomAD: NR

AdditionalInfo: His heart pumping ability was 30%. He received a defibrillator and was considered for a heat transplant. He also had a second gene change in TTN.

Case#: 3 Patient II-1 10 years

DiseaseAssertion: left ventricular noncompaction

FamilyInfo: Several family members have heart disease. One relative died from cardiac arrest at age 50.

ParentalTesting: NR

CasePresentingHPOs: NR

CaseHPOFreeText: The patient had extra ridges and deep spaces in his heart muscle. His ECG also showed changes in his heart's electrical activity.

CaseNotHPOs: NR

CaseNotHPOFreeText: Normal heart muscle thickness and normal heart pumping ability.

CasePreviousTesting: ECG, heart monitoring, heart ultrasound, heart biopsy and genetic testing

Genotyping Method: NGS and sanger sequencing

FunctionalAnalysis:computer testing suggested the ACTC1 gene change could weaken the protein.

Variant: NM_005159.4:c.62C>T

Clinvar: 410264

CAID: CA16614451

gnomAD: NR

AdditionalInfo: His heart pumping ability was 63%.He received medication and remained stable during follow up.

Case#: 4 Patient III-2 14 years

DiseaseAssertion: HCM and LVNC

FamilyInfo: Several family members have heart disease. One relative died from cardiac arrest at age 50.

ParentalTesting: NR

CasePresentingHPOs: NR

CaseHPOFreeText: The patient had thickened heart muscle extra ridges and deep spaces in his heart, and episodes of fast or abnormal hearbeats.

CaseNotHPOs: NR

CaseNotHPOFreeText: Heart MRI did not show sign of heart muscle scarring

CasePreviousTesting: ECG, heart monitoring, heart ultrasound, heart biopsy and genetic testing

Genotyping Method: NGS and sanger sequencing

FunctionalAnalysis:computer testing suggested the ACTC1 gene change could weaken the protein.

Variant: NM_005159.4:c.62C>T

Clinvar: 410264

CAID: CA16614451

gnomAD: NR

AdditionalInfo: His heart pumping ability was 60%.He received medication and remained stable during follow up.

Case#: P16, 17 year old male

DiseaseAssertion: left ventricular noncompaction cardiomyopathy

FamilyInfo: His mother, sister, and grandfather on his mothers side also had LVNC

ParentalTesting: NR

CasePresentingHPOs: NR

CaseHPOFreeText: The patient had an abnormal structure in the left side of his heart. His heart ultrasound showed extra muscle ridges and deep spaces in the heart muscle.

CaseNotHPOs: NR

CaseNotHPOFreeText: The study did not report fainting, heart rhythm problems, blood clots, or heart failure for this patient.

CasePreviousTesting: Heart ultrasound, ECG, heart MRI, blood tests, and genetic testing.

Genotyping Method: Next generation sequencing followed by Sanger sequencing to confirm this gene change

FunctionalAnalysis: NR

Variant: NM_005159.5:c.329>T

Clinvar: 2137647

CAID: CA391631478

gnomAD: Exact frequency not provided

AdditionalInfo: The patient's heart pumping ability was 70 %on ultrasound. Researchers classified his ACTC1 variant as a variant of uncertain significance meaning they were not sure whether it causes diseases.

CaseIII-3: female

DiseaseAssertion: LVNC, Ebstin anomaly, congenital heart disease

FamilyInfo: all mutation carriers have LVNC, with some having Ebstein anomaly and/or other CHD

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting:

GenotypingMethod:

Variant: NM_000257.4:c.847T>G

ClinVar: 66081

CAID: CA016893

gnomAD:

Case#: WPW381

DiseaseAssertion: WPW, LY non compaction cardiomyopathy

FamilyInfo: inherited

CasePresentingHPOs: Wolff-Parkinson-White syndrome, Left ventricular noncompaction cardiomyopathy (HP:0001716, HP:0011664)

CaseHPOFreeText: 0 ARIC, 0 THou, 8.12e-6 gnomAD, 8.24e-6 Exac, 0 esp6500, 34 CADD_phred, 0 pLI,

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: ECG, exome sequencing, gene analysis, burden analysis,

Variant: NM_000257.4(MYH7):c.728G>A (p.Arg243His)

ClinVar: 14126 https://www.ncbi.nlm.nih.gov/clinvar/variation/14126/

CAID: N/A

gnomAD: 0.00002891 Latino/Admixed American https://gnomad.broadinstitute.org/variant/14-23894525-C-T

Case1: 49 year old male

DiseaseAssertion: LVNC

FamilyInfo: parent to child transmission affecting both sexes in ≥2 successive generations

CasePresentingHPOs: HP:0001650

"Aortic valve stenosis"

CaseHPOFreeText: bicuspid aortic valve (BAV) and mild-to-moderate aortic valvular stenosis, grade III/VI harsh crescendo-decrescendo murmur at right upper sternal border radiating to both carotids, prominent trabeculations, left ventricular apical recesses in continuation with the ventricular cavity, reduced LV systolic function with concomitant LV dilation

GenotypingMethod: next-generation sequencing using an Illumina Solexa platform for the coding regions including the splice sites of 27 genes known to be associated with familial dilated cardiomyopathy

Variant: NM_000257.4:c.1316T>G

ClinVar: 181406

CAID: CA010528

gnomAD: not found

CaseII2: 19 year old male, Chinese

DiseaseAssertion: LVNC

FamilyInfo: Mother met diagnostic criteria for LVNC but was asymptomatic, cardiopath diagnosed brother suffered sudden death at age 13

CasePresentingHPOs: HP:0001962

"Palpitations"

CasePreviousTesting: Echocardiography

GenotypingMethod: Whole Exome Sequencing and mutation screening, SPRING used to prioritize the disease-causing nonsynonymous single nucleotide variants (SNVs) in exome sequencing, Sanger sequencing confirmed cosegregation of the mutations in pedigree

Variant: NM_000257.3:c.1492C>G

identified 13 SNVs with P < 0.05 (Table 1). MYH7 (c.C1492G), DSP (c.A2360G), RICTOR (c.C629T) and PRMT3 (c.T500C) all show P < 0.01 but only MYH7 (c.C1492G) reach significant criterion with P of 3.45E− 05 and q-value of 4.65E− 03.

ClinVar: not found

CAID: CA389050478

gnomAD: not found

FamilyB

DiseaseAssertion: Left ventricular noncompaction (LVNC)

FamilyInfo: Presenting LVNC, Identified rare, protein changing mutations in MYH7, none of which have been previously reported but all of which were predicted to be pathogenic with multiple in silico prediction algorithms

GenotypingMethod: Whole exome sequencing analysis

Variant: NM_000257.4:c.1943C>T

ClinVar: not found

CAID: CA389049480

gnomAD: not found

FamilyE

DiseaseAssertion: Left ventricular noncompaction (LVNC)

FamilyInfo: Presenting LVNC, Identified rare, protein changing mutations in MYH7, none of which have been previously reported but all of which were predicted to be pathogenic with multiple in silico prediction algorithms

GenotypingMethod: Whole exome sequencing analysis

Variant: NM_000257.4:c.2099A>G

ClinVar: not found

CAID: CA389049130

gnomAD: not found

FamilyD

DiseaseAssertion: Left ventricular noncompaction (LVNC)

FamilyInfo: Presenting LVNC, Identified rare, protein changing mutations in MYH7, none of which have been previously reported but all of which were predicted to be pathogenic with multiple in silico prediction algorithms

GenotypingMethod: Whole exome sequencing analysis

Variant: NM_000257.4:c.488A>C

ClinVar: not found

CAID: CA389052716

gnomAD: not found

Case#: 30

DiseaseAssertion: LVNC

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: 3.31 fathom, 0.002 sift, 0.997 polyphen, 0 GVGD, mutation taster 1, -2.08 provean, -4.22 CADD

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: physical examination, ECG, variant screening and classification, genic collapsing test, group statistical analysis

Variant: NM_000257.4(MYH7):c.67C>T (p.Arg23Trp)

ClinVar: 181295 https://www.ncbi.nlm.nih.gov/clinvar/variation/181295/

CAID: N/A

gnomAD: 0.00007961 European/Finnish https://gnomad.broadinstitute.org/variant/14-23902875-G-A

Case#: 28

DiseaseAssertion: LVNC

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: 7 sift, 0.969 polyphen, C65 GVGD, mutation taster 1, -4.06 provean, -6.25 CADD

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: physical examination, ECG, variant screening and classification, genic collapsing test, group statistical analysis

Variant: NM_000257.3:c.1859T>C

ClinVar: absent

CAID: CA389049669

gnomAD: absent

Case#: 16, female, diagnosed as fetus,

DiseaseAssertion: LVNC

FamilyInfo: yes

CasePresentingHPOs: cyanosis, Ebstein anomaly of the tricuspid valve, Ventricular septal defect, coarctation of aorta, congestive heart failure (HP:0000961, HP:0010316, HP:0001629, HP:0001680, HP:0001635)

CaseHPOFreeText: -5.47 Fathmm, 0 sift, 0.001 polyphen2, 0 GVGD, mutation taster 1, -3.64 provean, -5.15 CADD,

CaseNotHPOs: N/A

CaseNotHPOFreeText: no extracardiac abnormalities

CasePreviousTesting: N/A

CaseGenotypingMethod: physical examination, ECG, variant screening and classification, genic collapsing test, group statistical analysis

Variant: absent

ClinVar: absent

CAID: CA389051391 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051391

gnomAD: absent

Case#: 27

DiseaseAssertion: LVNC

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: 1.96 Fathmm, 0 sift, 0.997 polyphen2, C65 GVGD, mutation taster 1, -4.85 provean, -5.29 CADD

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: physical examination, ECG, variant screening and classification, genic collapsing test, group statistical analysis

Variant: NM_000257.3:c.2078T>G

ClinVar: absent

CAID: CA389049168

gnomAD: absent

Case#: 18, female, diagnosed at 4 days,

DiseaseAssertion: LVNC

FamilyInfo: yes

CasePresentingHPOs: heart murmur, Ebstein anomaly of the tricuspid valve, Ventricular septal defect, coarctation of aorta, Congestive heart failure (HP:0030148, HP:0010316, HP:0001629, HP:0001680, HP:0001635)

CaseHPOFreeText: -5.47 Fathmm, 0 sift, 0.001 polyphen2, 0 GVGD, mutation taster 1, -3.64 provean, -5.15 CADD,

CaseNotHPOs: N/A

CaseNotHPOFreeText: no extracardiac abnormalities

CasePreviousTesting: N/A

CaseGenotypingMethod: physical examination, ECG, variant screening and classification, genic collapsing test, group statistical analysis

Variant: NM_000257.3:c.1085T>G

ClinVar: absent

CAID: CA389051391 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA389051391

gnomAD: absent

Case#: 24

DiseaseAssertion: LVNC

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: 5.9 Fathmm, 0 sift, 0.984 polyphen2, 0 GVGD, mutation taster 1, -4.96 provean, -6.07 CADD

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: physical examination, ECG, variant screening and classification, genic collapsing test, group statistical analysis

Variant: NM_000257.4(MYH7):c.689T>C (p.Phe230Ser)

ClinVar: 263543 https://www.ncbi.nlm.nih.gov/clinvar/variation/263543/

CAID: N/A

gnomAD: absent

Case: proband, 2mo

DiseaseEntity: Left ventricular noncompaction (LVNC)

CasePresentingHPOs: HP:0001635 (congestive heart failure)

HPOsFreeText: required mechanical ventilation and inotropic support, depressed left ventricular function, deep left ventricle trabeculations

FamilyInfo: sibling with fetal demise at 24wks gestation due to pulmonary hypoplasia and biventricular noncompaction with deep recesses in myocardial walls of both ventricles, right ventricular dilation, and widespread fibrosis; signs of LVNC also present in 4yo sibling and father, paternal grandfather had history of arrhythmia

CaseGenotypingMethod: WES

Variant: NM_000257.4(MYH7):c.1159C>T (p.Leu387Phe)

ClinVar: 524975, https://www.ncbi.nlm.nih.gov/clinvar/variation/524975/

gnomAD: absent from gnomAD

MultipleGeneVariants:

(1) MLK2 Variant

Variant: NM_001308142.1:c.2010G>C

CAID: CA394829003, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA394829003

gnomAD: absent

(2) NKX2-5 Variant

Variant: NM_004387.4(NKX2-5):c.355G>T (p.Ala119Ser)

ClinVar: 9018, https://www.ncbi.nlm.nih.gov/clinvar/variation/9018/

gnomAD: 0.0009792, https://gnomad.broadinstitute.org/variant/5-172660192-C-A?dataset=gnomad_r2_1

Case1: Male

DiseaseAssertion: HCM and LVNC

FamilyInfo: daughter with same diagnoses and variant 1

Variant1: NM_000257.4:c.1859T>C

ClinVar: not found

CAID: CA389049669

gnomAD: not found

Variant2: NM_000257.4:c.4377G>T

ClinVar: 43012

CAID: CA014901

gnomAD: https://gnomad.broadinstitute.org/variant/14-23886504-C-A?dataset=gnomad_r2_1

0.0005349 European (non Finnish)

Case1: 42 year old male

DiseaseAssertion:DCM and LVNC

FamilyInfo: Same mutation in proband found in father, sister, and daughter

CasePreviousTesting: Sanger sequencing of coding exons and flanking intronic regions of the main sarcomeric genes, including MYH7, MYBPC3, TNNT2, TNNI3, TPM1, ACTC, MYL2, MYL3 and TNNC.

GenotypingMethod: NGS, Sanger sequencing

Variant: NM_000257.4:c.2146G>A

ClinVar: 14105

CAID: CA011770

gnomAD: not found

Case120682: 62 year old Caucasian female

DiseaseAssertion: LVNC

FamilyInfo: family history was negative for cardiomyopathy or CHF, one daughter was noted to have a persistent high resting pulse

CasePresentingHPOs:

CaseHPOFreeText: first degree AV-block on ECG and prominent trabeculations at the left ventricular (LV) apex, mild aortic regurgitation

CaseNotHPOs:

CaseNotHPOFreeText:pulmonary hypertension

CasePreviousTesting: 41 cardiomyopathy-associated genes

GenotypingMethod: next generation sequencing and variant analysis, WES or WGS

Variant: NM_000257.4:c.732+1G>A

ClinVar: 14127

CAID: CA016715

gnomAD: 0.00005437 East Asian

https://gnomad.broadinstitute.org/variant/14-23900793-C-T

Case1: 3 year old female

DiseaseAssertion: LVNC

FamilyInfo: sister and brother diagnosed with Ebstein's anomaly, LVNC, and VSD, and same novel mutation was identified in sister, brother, and father

CasePresentingHPOs: HP:0031664, HP:0010316, HP:0001631, HP:0002789, HP:0001649, HP:0001680

"Systolic heart murmur, Ebstein anomaly of the tricuspid valve, Atrial septal defect, Tachypnea, Tachycardia, Coarctation of aorta

CaseHPOFreeText: precordial systolic murmur at 4 days old, moderate tricuspid valve insufficiency, right heart enlargment, membranous VSD, feeding poorly at 11 days

CasePreviousTesting: No mutations were identified in the TAZ, LMNA/C, MYBPC3, TNNT2, TNNI3, ACTC, and TPM1 genes

GenotypingMethod: Sequence analysis of MYH7

Variant: NM_000257.4:c.1085T>G

ClinVar: not found

CAID: CA389051391

gnomAD: not found

Case1: male fetus

DiseaseAssertion: LVNC

FamilyInfo: first two pregnancies had resulted in miscarriages due to cervical insufficiency. The third pregnancy (after cerclage) resulted in a healthy nondysmorphic female with mild Ebstein anomaly of the tricuspid valve. The father was reported to have a history of a cardiac murmur and possible “hole in the heart.” Fetal echocardiography revealed that our patient's second child (fourth pregnancy) also had mild Ebstein anomaly. Father also has Ebstein anomaly, with significant apical displacement of the tricuspid valve, moderate tricuspid valve insufficiency, and right heart enlargement

CasePresentingHPOs: HP:0010316, HP:0031195

"Ebstein anomaly of the tricuspid valve, Apical hypertrabeculation of the left ventricle"

CaseHPOFreeText: mild apical displacement of the tricuspid valve, presence of multiple trabeculations on parasternal short‐axis and apical 4‐chamber views, with deep intertrabecular recesses

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: echocardiogram, Peripheral blood samples use to test 46 genes initially (including MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1)

GenotypingMethod: Testing was performed by oligonucleotide‐based target capture, followed by next generation sequencing. Sanger sequencing was used to provide data in areas with insufficient coverage and confirm clinically significant and novel variants. Heterozygous.

VariantMYH7: NM_000257.4:c.3658_3660del

ClinVar: 42968

CAID: CA013921

gnomAD: not reported

**VariantTTN: c.25722_25724delAGA (p.Glu8576del)

Allele registry currently not working

CaseII2: 65 year old male

DiseaseAssertion: left ventricular non compaction cardiomyopathy

FamilyInfo: three family members presenting with the same MYH7 mutation

CasePresentingHPOs: HP:0012764, HP:0002515, HP:0003376, HP:0003307, HP:0003391, HP:0003547

"Orthopnea, Waddling gait, Steppage gait, Hyperlordosis, Gowers sign, Shoulder girdle muscle weakness"

CaseHPOFreeText: shortness of breath during exertion, foot drop, At lower limbs weakness and hypotrophy were severe in distal muscles and moderate in proximal muscles

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: molecular analysis for ACTA1 and ITGA7 was performed, resulted negative. Molecular analysis for DES, LMNA and MYH7 genes were carried out

GenotypingMethod: mutation screening, primers flanking the intron-exon junctions of each MYH7 exon, the 5′ and 3′ UTR

Variant: NM_000257.4:c.5401G>A

ClinVar: 43069

CAID: CA016087

gnomAD: not found

CaseV-4: Female, 11 years old

DiseaseAssertion: CFTD and LVNC

FamilyInfo: Multigenerational Italian family. Phenotypic data were available for 10 individuals (3 males and 7 females) ranging in age from 4 to 50 years old. All individuals were of Caucasian ancestry. DNA was available for 6 individuals (IV-10, IV-13, IV-14, V-1, V-4, V-5). Authors identified a mild LVNC phenotype in the mother (IV-14), sister (V-5) and cousin (V-1) of the proband, with hypertabeculations of the mid inferolateral wall and of the ape and without neuromuscular disorders. During the growth, there was a reduction of clinical signs in patients V-1 and V-5. No data have been collected for individual IV-9, who died at the age of 35 of unknown causes. The father (IV-13) of the proband was asymptomatic.

Proband is the first child of a family with a history of consanguinity (mother’s parents are first-degree cousins) and diabetes in the maternal line (grandmother, one great-uncle, one uncle and a first-degree cousin) without neuromuscular diseases.

LVNC segregated as a dominant mode of inheritance with high phenotypic heterogeneity and reduced penetrance. CFTD phenotype showed a recessive mode of inheritance.

CasePresentingHPOs: HP:0001290, HP:0002033, HP:0001643, HP:0001655, HP:0001374, HP:0004325, HP:0001943, HP:0001508, HP:0002515, HP:0002650, HP:0001284

"Generalized hypotonia, poor suck, Patent ductus arteriosus, Patent foramen ovale, Congenital hip dislocation, Decreased body weight (below 3rd percentile), Hypoglycemia, Failure to thrive, waddling gait, Scoliosis, Areflexia

CaseHPOFreeText: persistent crying, Persistent arterial duct and patent foramen ovale were diagnosed at birth but resolved spontaneously, as shown by echocardiography at the age of 1 month, congenital dislocation of the left hip, at 17 months of age hospitalized due to body weight below the third percentile and hypoglycemia, difficulties in chewing and swallowing, inability to stand up from a sitting position, a slight degree of weakness of the facial and masticator muscles, mild weakness of the glutei and ileo-psoas and marked bilateral quadriceps, Tendon reflexes were absent. Joints contractures had never been observed, A blood test confirmed hypoglycemia and normal levels of serum creatine kinase and isoenzymes, quadriceps muscle biopsy displayed a predominance of type 1 fibers

CaseNotHPOs:

CaseNotHPOFreeText: internal nuclei, nemaline bodies, cores were observed

CasePreviousTesting: Authors extended the clinical and instrumental (EMG, ECG, Echocardiography, muscle biopsy) evaluation to the whole family, Echocardiography showed a slight left ventricular (LV) dilatation, a moderate reduction of the LV global function (ejection fraction 40%), and a non-compacted aspect of the overall infero-lateral wall. The karyotype and FISH were normal. The serum creatine kinase (CK) was within the normal range, Dystrophin, emerin, calpain and lamin A/C were examined and found to be normal, cardiological investigation confirmed a long QTc and showed signs of left ventricular hypertrophy and repolarization abnormalities in the ECG, performed a thorough survey of all previously identified CFTD and LVNC genes to definitively exclude their involvement in the disease phenotype. Only intronic polymorphic variants were detected in TPM3, ACTA1, TPM2, MYL2, MYL3, G4.5, DTNA, ZASP, ACTC1, MYBPC3 and TMP1. Both intronic and coding polymorphic variants were detected in SEPN1, RYR1, MYH7, LMNA/C, TNNT2 and TNNI3

GenotypingMethod: Whole-exome sequencing of the proband and her cousin

VariantMYH7B: NM_020884.5:c.2668C>T

ClinVar:

CAID: CA9827409

gnomAD: https://gnomad.broadinstitute.org/variant/20-33582046-C-T