Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002365 | SCV001160272 | uncertain significance | not specified | 2019-02-20 | criteria provided, single submitter | clinical testing | The MYH14 c.2528A>G; p.Tyr843Cys variant (rs373457292), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found in the African population with an overall allele frequency of 0.04% (10/22910 alleles) in the Genome Aggregation Database. The tyrosine at codon 843 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Tyr843Cys variant is uncertain at this time. |
Invitae | RCV001860514 | SCV002312236 | uncertain significance | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 843 of the MYH14 protein (p.Tyr843Cys). This variant is present in population databases (rs373457292, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MYH14-related conditions. ClinVar contains an entry for this variant (Variation ID: 811897). 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 with a positive predictive value of 80%. 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. |