Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV000208372 | SCV000264076 | likely pathogenic | Primary familial hypertrophic cardiomyopathy | 2015-11-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001210689 | SCV001382187 | uncertain significance | Hypertrophic cardiomyopathy | 2019-06-20 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 263 of the MYH7 protein (p.Ile263Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant has been observed in in individuals affected with hypertrophic cardiomyopathy (PMID: 15358028, 27532257). ClinVar contains an entry for this variant (Variation ID: 181326). 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 disrupts the p.Ile263 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9829907, 24093860, 27247418, 27532257, 21425739, 12707239, 15008060). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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"). |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000223688 | SCV000280381 | uncertain significance | not specified | 2015-08-26 | 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. MYH7 p.Ile263Met (c.789A>G) The variant has been seen in at least one case. This variant was reported for by van Driest et al (2004) in a patient from their American HCM cohort. We could find no other reports. There is no segregation or functional data available on the variant. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. The isoleucine at codon 263 is conserved across species, as are neighboring amino acids. Other variants have been reported in association with disease at this codon (p.Ile263Thr, which we consider likely disease causing) and a nearby codon (p.Gly256Glu). In total the variant has not been seen in ~5600 published controls and publicly available population datsets. There is no variation at codon 263 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~5500 Caucasian and African American individuals (as of 1/16/2012). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 1/16/2012). The variant was not observed in the following published control samples: 200 (van Driest et al 2004). |