ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.2269C>T (p.Pro757Ser) (rs200827630)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456783 SCV000541349 uncertain significance Alstrom syndrome 2016-05-26 criteria provided, single submitter clinical testing This sequence change replaces Pro with Ser at codon 758 of the ALMS1 protein (p.Pro758Ser). The Pro residue is conserved and there is a physicochemical difference between Pro and Ser. This variant is present in population databases (rs200827630, ExAC 0.008%) but has not been reported in the literature in individuals with a ALMS1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "tolerated"; PolyPhen-2: ""; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001731684 SCV001982367 uncertain significance not provided 2021-09-24 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016)
Natera, Inc. RCV000456783 SCV001458912 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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