Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158086 | SCV000208021 | pathogenic | not provided | 2020-09-21 | criteria provided, single submitter | clinical testing | Reported in patients with HCM in the published literature (Agarwal et al., 2015; Walsh et al., 2017; Viswanathan et al., 2017); Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27532257, 26271555, 29121657) |
Ambry Genetics | RCV002390378 | SCV002695900 | pathogenic | Cardiovascular phenotype | 2019-11-20 | criteria provided, single submitter | clinical testing | The p.W486* pathogenic mutation (also known as c.1457G>A), located in coding exon 16 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 1457. This changes the amino acid from a tryptophan to a stop codon within coding exon 16. This alteration has been reported in association with hypertrophic cardiomyopathy (HCM) (Walsh R et al. Genet. Med., 2017 02;19:192-203; Viswanathan SK et al. PLoS ONE, 2017 Nov;12:e0187948). 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 | RCV003586149 | SCV004294807 | pathogenic | Hypertrophic cardiomyopathy | 2023-12-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp486*) 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 individual(s) with hypertrophic cardiomyopathy (PMID: 27532257, 29121657). ClinVar contains an entry for this variant (Variation ID: 180937). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |