Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000604027 | SCV000711108 | uncertain significance | not specified | 2017-10-26 | criteria provided, single submitter | clinical testing | The p.Arg1565Gln variant in MYH14 has not been previously reported in individual s with hearing loss, but has been identified in 1/1622 East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSN P rs374911327). Although this variant has been seen in the general population, i ts frequency is not high enough to rule out a pathogenic role. Computational pre diction tools and conservation analysis do not provide strong support for or aga inst an impact to the protein. In summary, the clinical significance of the p.Ar g1565Gln variant is uncertain. ACMG/AMP Criteria applied: PM2 (Richards 2015). |
Invitae | RCV002532724 | SCV003480078 | uncertain significance | not provided | 2022-10-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 504618). 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. 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 MYH14 protein function. This variant has not been reported in the literature in individuals affected with MYH14-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1524 of the MYH14 protein (p.Arg1524Gln). |