Table 3. Clinical and variant information for VCL pLOF probands and family members with DCM.
All VCL variants are reported in NM_014000.2. Infantile: age at testing ≤ 1 year; Childhood: age at testing >1 year and ≤10 years; Adolescent >10 years and ≤20 years; Adult: age at testing >20 years
| Proband | Family ID. Position in Pedigree | Age at Testing | Sex | Clinical Information | VCL pLOF Variant Identified | Max Allele Frequency in gnomAD (v2.1) | Additional Variant(s) Identified | Classification of Add’l Variant(s) |
|---|---|---|---|---|---|---|---|---|
| 1 | A. II-1 | Infantile | M | DCM and VT | c.1639C>T p.Arg547* | 0.00009 (1/113,732 alleles) in European Population | DSP: c.943C>T p.Arg315Cys | VUS |
| A. II-2 | Infantile | F | Mildly decreased cardiac function | c.1639C>T p.Arg547* | 0.00009 (1/113,732 alleles) in European Population | DSP: c.943C>T p.Arg315Cys – Not Detected | ||
| 2 | B. II-1 | Childhood | F | DCM or myocarditis with adenovirus and RSV infections at time of diagnosis; stable myocardial dysfunction at follow up | c.1713delA p.Ala573Hisfs*8 | 0.0007 (7/10,076 alleles) in Ashkenazi Jewish Population | MYH7: c.2063delT p.Leu688Argfs*38 | LP (recessive) |
| 3 | C. III-1 | Infantile | F | DCM | c.562C>T p.Arg188* | 0.00003 (3/113,666 alleles) in European Population | ||
| 4 | D. II-1 | Infantile | F | DCM | c.313C>T p.Arg105* | 0.00005 (1/18,388 alleles) in East Asian Population | LAMA4: c.2619G>T p.Gln873His | VUS |
| 5 | E. II-1 | Infantile | M | DCM | c.1762C>T p.Gln588* | Absent | ||
| 6 | F. III-1 | Adolescent | M | DCM and VT | c.659dupA p.Asn220Lysfs*21 | 0.00007 (1/15,330 alleles) in European Population | LAMA4: c.4031A>G p.Lys1344Arg | VUS |
| TPM1: c.97G>A p.Glu33Lys | VUS | |||||||
| 7 | G. III-2 | Infantile | M | DCM | c.1544−2A>G | Absent | MYH7: c.2347C>G p.Arg783Gly | LP |
| G. I-2 | Adult | F | DCM | c.1544−2A>G | Absent | MYH7: c.2347C>G p.Arg783Gly | ||
| G. II-2 | Adult | F | DCM | c.1544−2A>G (obligate carrier) | Absent | MYH7: c.2347C>G p.Arg783Gly (obligate carrier) | ||
| 8 | Infantile | M | DCM | c.670dupG p.Glu224Glyfs*17 | Absent | |||
| 9 | Adolescent | M | DCM | c.2828_2829delCT p.Pro943Argfs*9 | 0.0005 (12/24,968 alleles) in African Population | RYR2: c.2786G>A p.Arg929His | VUS | |
| 10 | Infantile | F | DCM | c.3163C>T p.Arg1055* | Absent | |||
| 11 | H. II-1 | Adolescent | F | DCM | c.3115C>T p.Gln1039* | Absent | ||
| H. I-2 | Adult | M | DCM | c.3115C>T p.Gln1039* | Absent | |||
| 12 | Adolescent | M | Moderate LV dilation with normal cardiac function four years later | c.2131+1delG | Absent | |||
| 13 | I. II-1 | Infantile | F | Neonatal DCM that improved to mild LV dilation at follow up | c.2435−1G>A | Absent | SCN5A: c.1844G>A p.Gly615Glu | VUS |
| I. I-2 | Adult | F | Episode of chest pain and normal QT interval | Negative | N/A | SCN5A: c.1844G>A p.Gly615Glu | VUS | |
| I. II-2 | Childhood | M | Asymptomatic but prolonged QT interval | Negative | N/A | SCN5A: c.1844G>A p.Gly615Glu | VUS | |
| I. II-3 | Childhood | F | Asymptomatic but prolonged QT interval | c.2435−1G>A | Absent | SCN5A: c.1844G>A p.Gly615Glu | VUS | |
| I. II-4 | Childhood | M | Asymptomatic but prolonged QT interval | Not Tested | N/A | SCN5A: c.1844G>A p.Gly615Glu | VUS | |
| 14 | Childhood | M | DCM | c.2828_2829delCT p.Pro943Argfs*9 | 0.0005 (12/24,968 alleles) in African Population | Unspecified* | VUS | |
| 15 | Childhood | F | DCM | c.562C>T p.Arg188* | 0.00003 (3/113,666 alleles) in European Population | |||
| 16 | Adult | M | DCM | c.2005C>T p.Arg669* | 0.00005 (1/18,348 alleles) in East Asian Population | Unspecified* | VUS | |
| 17 | Infantile | F | DCM | c.1543+1G>T | Absent | |||
| 18 | Adult | F | DCM | c.241_622+1dup | Absent | ACTC1: c.602C>T p.Ser201Phe | VUS | |
| 19 | Infantile | F | Severe left ventricular dilation with impaired function and acute heart failure | c.2331del p.Lys778Serfs*6 | Absent |
*
Detailed information for additional variants identified was not available for all probands due to IRB restrictions.
M: male; F: female; pLOF: putative loss of function; DCM: dilated cardiomyopathy; VT: ventricular tachycardia; LV: left ventricular; VUS: variant of uncertain significance; LP: likely pathogenic; RSV: respiratory syncytial virus.