Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035972 | SCV000059624 | uncertain significance | not specified | 2017-01-25 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
Invitae | RCV001852733 | SCV002256952 | uncertain significance | Hypertrophic cardiomyopathy | 2021-10-28 | 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. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 43077). This missense change has been observed in individual(s) with hypertrophic caardiomyopathy (PMID: 27247418). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 187 of the MYH7 protein (p.Asn187Ser). |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000035972 | SCV000280369 | uncertain significance | not specified | 2015-05-27 | 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.Asn187Ser (c.560 A>G) in the MYH7 gene. The variant is still novel (as of January 6th, 2015). This is a conservative amino acid change with a neutral, polar serine replaced with a neutral, polar asparagine. The serine at position 187 is highly conserved across species. In silico analysis by LMM using the recently developed sarcomere-specific PolyPhen2 predicts the variant to be pathogenic. This tool has a reported accuracy of 94% when predicting a variant to be pathogenic (Jordan et al 2011). Another variant at this codon (p.Asn187Lys), and other variants in surrounding codons (p.Val186Leu, p.Thr188Asn, p.Arg190Thr, p.Ala196Thr) have been reported in association with cardiomyopathy. There is no variation at codon 187 listed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of January 6th, 2015). |