ClinVar Miner

Submissions for variant NM_013432.5(TONSL):c.1958C>T (p.Thr653Met)

gnomAD frequency: 0.00001  dbSNP: rs755055463
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001788438 SCV002031211 uncertain significance not provided 2021-05-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 30773277)
Labcorp Genetics (formerly Invitae), Labcorp RCV001788438 SCV003483989 uncertain significance not provided 2022-06-25 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 653 of the TONSL protein (p.Thr653Met). This variant is present in population databases (rs755055463, gnomAD 0.007%). This missense change has been observed in individual(s) with spondylometaphyseal dysplasia (PMID: 30773277). ClinVar contains an entry for this variant (Variation ID: 982207). 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.
University of Washington Center for Mendelian Genomics, University of Washington RCV001261769 SCV001439085 likely pathogenic Skeletal dysplaisia with extra-skeletal manifestations no assertion criteria provided research

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