ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3019T>C (p.Trp1007Arg)

dbSNP: rs730880585
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158208 SCV000208143 uncertain significance not provided 2020-11-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); 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: 27532257, 25086479)
Invitae RCV001225864 SCV001398158 uncertain significance Hypertrophic cardiomyopathy 2022-10-12 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1007 of the MYBPC3 protein (p.Trp1007Arg). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 25086479, 27532257, 33782553). 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 180996).
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000223707 SCV000280255 uncertain significance not specified 2011-11-30 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Trp1007Arg (W1007R; c.3019T>C) in the MYBPC3 gene. This variant is novel. It has not been reported in association with HCM to date. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging (score: 1.00). Mutation taster predicts this change to be damaging with a score of 101. SIFT predicts this change to be damaging with a median information content of 3.12. The Tryptophan at codon 1007 is conserved across species, as are neighboring amino acids. No other variants have been reported in association with disease at this codon and nearby codons. This is a conservative amino acid change with a non polar, neutral Tryptophan replaced with a polar, positive Arginine In total the variant has not been seen in 6,900 published controls and individuals from publicly available population datasets. Familion reports this variant has not been observed in an internal control population of over 400 unrelated, ethnically diverse individuals. There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 5/2/13). There is no variation at codon 1007 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on 6,500 Caucasian and African American individuals (as of 5/2/13). Note that this dataset does not match the patient's ancestry.

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.