ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.3883C>T (p.Arg1295Trp)

gnomAD frequency: 0.00007  dbSNP: rs372367091
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001133312 SCV001293006 uncertain significance Autosomal dominant nonsyndromic hearing loss 4A 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics RCV002556862 SCV003684785 uncertain significance Inborn genetic diseases 2022-05-11 criteria provided, single submitter clinical testing The c.3760C>T (p.R1254W) alteration is located in exon 28 (coding exon 27) of the MYH14 gene. This alteration results from a C to T substitution at nucleotide position 3760, causing the arginine (R) at amino acid position 1254 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Invitae RCV003718352 SCV004515979 uncertain significance not provided 2023-10-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1254 of the MYH14 protein (p.Arg1254Trp). This variant is present in population databases (rs372367091, gnomAD 0.03%). 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: 893947). 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 not expected to disrupt MYH14 protein function. 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.

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