ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.6382C>T (p.Pro2128Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689998 SCV000817671 uncertain significance Alstrom syndrome 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2128 of the ALMS1 protein (p.Pro2128Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs771800459, ExAC 0.002%). This variant has not been reported in the literature in individuals with 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: "Deleterious"; 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.
Integrated Genetics/Laboratory Corporation of America RCV000735888 SCV000864114 uncertain significance not specified 2018-11-19 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.6376C>T (p.Pro2126Ser, alternative name c.6382C>T) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.2e-05 in 276040 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6376C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (DSP c.5940dupC, p.Y1981fs*2), providing supporting evidence for a benign role. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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