Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000803525 | SCV000943403 | uncertain significance | Hypertrophic cardiomyopathy | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1260 of the MYH7 protein (p.Arg1260Trp). This variant is present in population databases (rs755386220, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 648727). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Color Diagnostics, |
RCV001177517 | SCV001341744 | uncertain significance | Cardiomyopathy | 2022-11-17 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 1260 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 7/251440 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Mayo Clinic Laboratories, |
RCV002261218 | SCV002541605 | uncertain significance | not provided | 2021-10-11 | criteria provided, single submitter | clinical testing |