ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.530C>T (p.Ser177Leu) (rs141204958)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000210886 SCV000264597 uncertain significance Malignant hyperthermia susceptibility 2015-12-01 criteria provided, single submitter research
Illumina Clinical Services Laboratory,Illumina RCV000755673 SCV000353166 benign Hypokalemic periodic paralysis 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455562 SCV000538561 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant has not been seen in affected patients before. MaxMAF is 0.07% (49 alleles - frequency too high for disorder). Variant is conserved in mammals.
Invitae RCV000651228 SCV000773079 uncertain significance Hypokalemic periodic paralysis 1; Malignant hyperthermia, susceptibility to, 5 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 177 of the CACNA1S protein (p.Ser177Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs141204958, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CACNA1S-related disease. ClinVar contains an entry for this variant (Variation ID: 199686). 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"; 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.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000755673 SCV000883077 uncertain significance Hypokalemic periodic paralysis 1 2018-11-21 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996101 SCV001150573 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing

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