Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV001195619 | SCV001366018 | uncertain significance | not specified | 2019-05-24 | criteria provided, single submitter | clinical testing | The p.Gln406Arg variant in MYH14 has not been previously reported in individuals with hearing loss, but has been identified in 0.05% (15/29730) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting. |
| Invitae | RCV003737025 | SCV004560320 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is expected to disrupt MYH14 protein function. ClinVar contains an entry for this variant (Variation ID: 930154). This variant has not been reported in the literature in individuals affected with MYH14-related conditions. This variant is present in population databases (rs552730148, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 398 of the MYH14 protein (p.Gln398Arg). |