ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.6362C>T (p.Thr2121Met)

gnomAD frequency: 0.00001  dbSNP: rs769205075
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Total submissions: 5
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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 RCV001195248 SCV001365555 uncertain significance not specified 2019-04-26 criteria provided, single submitter clinical testing The p.Thr2121Met variant in MYO7A has not been previously reported in individuals with hearing loss or Usher syndrome but has been identified in 0.008% (8/96196) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198381 SCV001369293 uncertain significance Autosomal dominant nonsyndromic hearing loss 11 2019-10-21 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.
Invitae RCV002560190 SCV003261727 uncertain significance not provided 2022-08-13 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 2121 of the MYO7A protein (p.Thr2121Met). This variant is present in population databases (rs769205075, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 929910). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV002560191 SCV003690694 uncertain significance Inborn genetic diseases 2022-08-31 criteria provided, single submitter clinical testing The c.6362C>T (p.T2121M) alteration is located in exon 47 (coding exon 46) of the MYO7A gene. This alteration results from a C to T substitution at nucleotide position 6362, causing the threonine (T) at amino acid position 2121 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001828608 SCV002088542 uncertain significance Usher syndrome type 1B 2020-05-15 no assertion criteria provided clinical testing

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