ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.3623C>T (p.Ala1208Val)

gnomAD frequency: 0.00005  dbSNP: rs758560911
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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.
GeneDx 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.