Submissions for variant NM_001145809.2(MYH14):c.5990C>T (p.Thr1997Met)

gnomAD frequency: 0.00010  dbSNP: rs201986144

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000213467	SCV000272012	uncertain significance	not specified	2015-05-07	criteria provided, single submitter	clinical testing	The p.Thr1997Met variant in MYH14 has not been previously reported in individual s with hearing loss, but has been identified in 7/46670 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 201986144). Computational prediction tools and conservation analyses do not prov ide strong support for or against an impact to the protein. In summary, the clin ical significance of the p.Thr1997Met variant is uncertain.
Illumina Laboratory Services, Illumina	RCV000306244	SCV000414462	uncertain significance	Autosomal dominant nonsyndromic hearing loss 4A	2018-01-13	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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001508872	SCV001715297	uncertain significance	not provided	2019-11-03	criteria provided, single submitter	clinical testing
Invitae	RCV001508872	SCV004260472	uncertain significance	not provided	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1956 of the MYH14 protein (p.Thr1956Met). This variant is present in population databases (rs201986144, gnomAD 0.01%). 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: 228882). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.