Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003586169 | SCV004296289 | uncertain significance | Hypertrophic cardiomyopathy | 2023-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 402 of the MYH7 protein (p.Pro402Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27247418). ClinVar contains an entry for this variant (Variation ID: 235025). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. 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. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000223772 | SCV000280293 | uncertain significance | not specified | 2012-06-27 | 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.Pro402Ser (c.1204C>T) in the MYH7 gene. The variant is novel. There is no listing in ClinVar (as of June 2nd, 2015) In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. The proline at codon 402 is conserved across species, as are neighboring amino acids. In total the variant has not been seen in ~6774 laboratory controls and individuals from publicly available population datasets. There is no variation at codon 402 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6500 Caucasian and African American individuals (as of March 5th, 2013). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of March 5th, 2013). GeneDx noted the variant was not seen in 274 presumably healthy individuals analyzed in their lab. There is no variation at codon 402 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 June 2nd, 2015). |