Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158264 | SCV000208199 | uncertain significance | not provided | 2023-03-16 | criteria provided, single submitter | clinical testing | Reported in one individual with DCM who also harbored the c.3490+1 G>T splice site mutation in the MYBPC3 gene (Hershberger R et al., 2010).; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 20215591) |
Invitae | RCV000468605 | SCV000546431 | uncertain significance | Hypertrophic cardiomyopathy | 2022-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1260 of the MYBPC3 protein (p.Gly1260Asp). This variant is present in population databases (rs730880606, gnomAD 0.1%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 20215591). This missense change has been observed to co-occur in individuals with a different variant in MYBPC3 that has been determined to be pathogenic (PMID: 20215591; Invitae), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 181025). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000158264 | SCV000925166 | uncertain significance | not provided | 2016-08-22 | no assertion criteria provided | provider interpretation |