Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621325 | SCV000740123 | pathogenic | Cardiovascular phenotype | 2017-02-07 | criteria provided, single submitter | clinical testing | The p.W1098* pathogenic mutation (also known as c.3294G>A), located in coding exon 30 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 3294. This changes the amino acid from a tryptophan to a stop codon within coding exon 30. This alteration has been reported in hypertrophic cardiomyopathy cohorts; however, clinical details were limited (Millat G et al. Eur J Med Genet, 2010 Jul;53:261-7; Lopes LR et al. Heart, 2015 Feb;101:294-301). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV001381667 | SCV001580159 | pathogenic | Hypertrophic cardiomyopathy | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp1098*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hypertrophic cardiomyopathy (PMID: 20624503, 23233322, 25031304, 31006259). ClinVar contains an entry for this variant (Variation ID: 520341). For these reasons, this variant has been classified as Pathogenic. |