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

gnomAD frequency: 0.00029  dbSNP: rs141204958

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CSER _CC_NCGL, University of Washington	RCV000210886	SCV000264597	uncertain significance	Malignant hyperthermia of anesthesia	2015-12-01	criteria provided, single submitter	research
Illumina Laboratory Services, Illumina	RCV000755673	SCV000353166	benign	Hypokalemic periodic paralysis, type 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, Mass General Brigham 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000651228	SCV000773079	likely benign	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2024-01-13	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000755673	SCV000883077	uncertain significance	Hypokalemic periodic paralysis, type 1	2018-11-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000996101	SCV001150573	uncertain significance	not provided	2024-03-01	criteria provided, single submitter	clinical testing	CACNA1S: PP3
Institute of Human Genetics, University of Leipzig Medical Center	RCV000755673	SCV001440196	uncertain significance	Hypokalemic periodic paralysis, type 1	2019-01-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000996101	SCV003800441	uncertain significance	not provided	2022-11-23	criteria provided, single submitter	clinical testing	The CACNA1S c.530C>T; p.Ser177Leu variant (rs141204958), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 199686). This variant is found in the non-Finnish European population with an allele frequency of 0.08% (98/128994 alleles) in the Genome Aggregation Database. The serine at codon 177 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.897). While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of the p.Ser177Leu variant is uncertain at this time.
Dept of Medical Biology, Uskudar University	RCV003318365	SCV004021955	uncertain significance	Long QT syndrome	2024-01-08	criteria provided, single submitter	research	Criteria: BS1, PP3