Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000614314 | SCV000713027 | uncertain significance | not specified | 2017-09-04 | criteria provided, single submitter | clinical testing | The p.Ala1208Val variant in MYH14 has not been previously reported in individual s with hearing loss, but has been identified in 8/72276 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs758560911). Although this variant has been seen in the general population, it s frequency is not high enough to rule out a pathogenic role. Computational pred iction tools and conservation analysis suggest that the p.Ala1208Val variant may impact the protein, though this information is not predictive enough to determi ne pathogenicity. In summary, the clinical significance of the p.Ala1208Val vari ant is uncertain. |
Gene |
RCV001591366 | SCV001823434 | likely benign | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001591366 | SCV003246800 | uncertain significance | not provided | 2022-04-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1167 of the MYH14 protein (p.Ala1167Val). 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 variant has not been reported in the literature in individuals affected with MYH14-related conditions. ClinVar contains an entry for this variant (Variation ID: 505662). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002529348 | SCV003529414 | uncertain significance | Inborn genetic diseases | 2022-11-08 | criteria provided, single submitter | clinical testing | The c.3500C>T (p.A1167V) alteration is located in exon 26 (coding exon 25) of the MYH14 gene. This alteration results from a C to T substitution at nucleotide position 3500, causing the alanine (A) at amino acid position 1167 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |