Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001222682 | SCV001394795 | uncertain significance | Hypertrophic cardiomyopathy | 2022-10-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 950875). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 23197398, 28771489). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 866 of the MYH7 protein (p.Ser866Pro). 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. |
Foundation for Research in Genetics and Endocrinology, |
RCV003226447 | SCV003922430 | uncertain significance | Hypertrophic cardiomyopathy 1 | 2023-05-05 | criteria provided, single submitter | clinical testing | A heterozygous missense variant in exon 22 of the MYH7 gene that results in the amino acid substitution of Proline for Serine at codon 866 (p.Ser866Pro) was detected. The observed variant has previously been reported in patients affected with hypertrophic cardiomyopathy. The p.Ser866Pro variant has not been reported in the 1000 genomes, gnomAD (v3.1), gnomdAD (v2) and topmed and databases. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as variant of uncertain significance. |