ClinVar Miner

Submissions for variant NM_017433.5(MYO3A):c.656C>T (p.Thr219Met)

gnomAD frequency: 0.00017  dbSNP: rs377660409
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000039048 SCV000062726 uncertain significance not specified 2012-12-11 criteria provided, single submitter clinical testing The Thr219Met variant in MYO3A has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Th r219Met variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. This variant has been identified in 0.04% (2/4406) of African American chromosomes in a broad population by the NHLBI Exom e sequencing project (http://evs.gs.washington.edu/EVS/). Although this variant has been seen in the general population, its frequency is not high enough to rul e out a pathogenic role. In summary, additional data is needed to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics RCV000764887 SCV000896047 uncertain significance Autosomal recessive nonsyndromic hearing loss 30 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV002513521 SCV003486421 uncertain significance not provided 2022-10-14 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs377660409, gnomAD 0.05%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 219 of the MYO3A protein (p.Thr219Met). ClinVar contains an entry for this variant (Variation ID: 45821). 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. 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.
Ambry Genetics RCV003352755 SCV004052455 uncertain significance Inborn genetic diseases 2023-08-15 criteria provided, single submitter clinical testing The c.656C>T (p.T219M) alteration is located in exon 8 (coding exon 6) of the MYO3A gene. This alteration results from a C to T substitution at nucleotide position 656, causing the threonine (T) at amino acid position 219 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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