Submissions for variant NM_000256.3(MYBPC3):c.1776G>A (p.Val592=)

dbSNP: rs727503196

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151116	SCV000198885	likely benign	not specified	2014-09-05	criteria provided, single submitter	clinical testing	Val592Val in exon 18 of MYBPC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. However, computational tools predict that th is variant may create of a novel 5' splice site, which if created would be expec ted to lead to an absent or truncated protein.
Ambry Genetics	RCV000617720	SCV000736433	likely benign	Cardiovascular phenotype	2017-07-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170952	SCV001333607	likely benign	Cardiomyopathy	2018-03-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001696180	SCV001916313	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003114298	SCV003788071	uncertain significance	Hypertrophic cardiomyopathy	2023-06-15	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 164100). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 592 of the MYBPC3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MYBPC3 protein.
PreventionGenetics, part of Exact Sciences	RCV004724929	SCV005337349	uncertain significance	MYBPC3-related disorder	2024-04-18	no assertion criteria provided	clinical testing	The MYBPC3 c.1776G>A variant is not predicted to result in an amino acid change (p.=). This variant is predicted to alter splicing based on available splicing prediction programs (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751; Alamut Visual Plus v1.6.1). However, the use of computer prediction programs is not equivalent to functional evidence. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.