Submissions for variant NM_000256.3(MYBPC3):c.1188G>T (p.Trp396Cys)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 3

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035374	SCV000059022	uncertain significance	not specified	2010-08-13	criteria provided, single submitter	clinical testing	The Trp396Cys variant has not been reported in the literature. Tryptophan (Trp) at position 396 is highly conserved across several evolutionary distant species , increasing the likelihood that the change is pathogenic.. This variant has bee n detected in our laboratory in a single proband of Indian descent. It should b e noted that this laboratory has only tested a small number of Indian probands s o far and therefore has very limited data on common variants that are found in t he Indian population. Future analysis could reveal that the Trp396Cys variant i s common in this population and therefore unlikely to be pathogenic. In summary , the clinical significance of this variant cannot be determined at this time.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798079	SCV002042118	uncertain significance	Cardiomyopathy	2020-04-01	criteria provided, single submitter	clinical testing
Invitae	RCV002513356	SCV003439702	uncertain significance	Hypertrophic cardiomyopathy	2022-07-27	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 42509). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (PMID: 27532257, 33673806). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 396 of the MYBPC3 protein (p.Trp396Cys). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.