Table 2.
Summary of Genetic Findings
| Pedigree | Gene | RefSeq | UCSC Genomic Position (GRCh37/hg19) |
Nucleotide Change* |
Amino Acid Change | Max ExAC MAF† | Max gnomAD MAF† | dbSNP | Bilineal Inheritance |
|---|---|---|---|---|---|---|---|---|---|
|
L |
LMNA | NM_170707.3 | chr1:156105707 | c.952G>A | p.(Ala318Thr) | 0 | 0.00003984 (NFE) |
rs267607574 | Possible versus de novo |
| BAG3 | NM_004281.3 | chr10:121429393 | c.211C>T | p.(Arg71Trp) | 0.0001348 (EAS) | 0.0001590 (EAS) |
rs387906874 | ||
| RBM20 | NM_001134363.2 | chr10:112541380 | c.1013T>C | p.(Met338Thr) | 0 | 0.00003519 (NFE) |
rs876657970 | ||
| TTN | NM_001267550.2 | chr2:179437290 | c.73568del | p.(Pro24523Hisfs*4) | 0 | 0 | n/a | ||
| DSP | NM_004415.3 | chr6:007585972 | c.8477G>A | p.(Arg2826His) | 0.000100624 (AFR) |
0 | rs548754771 | ||
|
N |
LMNA | NM_170707.3 | chr1:156106010 | c.1163G>A | p.(Arg388His) | 0.00001526 (NFE) |
0.00006498 (SAS) |
rs267607576 | Possible |
| RBM20 | NM_001134363.2 | chr10:112572302 | c.2205G>A | p.(Arg716Gln) | 0.0005057 (SAS) |
0.0003506 (SAS) |
rs375798246 | ||
|
O |
LMNA | NM_170707.3 | chr1:156106042 | c.1195C>T | p.(Arg399Cys) | 0.00001519 (NFE) |
0.00005808 (EAS) |
rs58672172 | Yes |
| TTN | NM_001267550.2 | chr2:179438190 | c.72669del | p.(Asp24224Ilefs*8) | 0 | 0 | rs727504531 | ||
|
P |
LMNA | NM_170707.3 | chr1:156106142- 156106143 |
c.1304_130 7dup |
p.(Ser437Hisfs*2) | 0 | 0.00003251 (SAS) |
rs267607577 | Presumptive |
| NEXN | NM_144573.3 | chr1:78401709 | c.1453G>A | p.(Glu485Lys) | 0.00008684 (AMR) | 0.0001108 (NFE) |
rs368812830 | ||
|
S |
LMNA | NM_170707.3 | chr1:156108540 | c.1960C>T | p.(Arg654*) | 0.000026 (NFE) | 0.00003698 (NFE) |
rs267607544 | Yes |
| PLN | NM_002667.3 | chr6:118880157 | c.73C>T | p.(Arg25Cys) | 0.00001501 (NFE) |
0.00008935 (AMR) | rs761056344 | ||
| MYPN | NM_001256267.1 | chr10:69881503 | c.308A>T | p.(Asp103Val) | 0.000172801 (AMR) |
0.0001489 (AMR) | rs758026056 |
*
By our application of the ACMG approach, all variants were classified as variants of uncertain significance23
†
The maximum non-Finnish minor allele frequency (MAF) and associated population for each variant is reported. A MAF of 0 implies absence of the variant from ExAC/gnomAD and sufficient coverage of the genomic position. Reported gnomAD results include both exomes and genomes. Abbreviations: AFR, African; AMR, Latino; EAS, East Asian; NFE, non-Finnish European; SAS, South Asian