Submissions for variant NM_000083.3(CLCN1):c.663G>A (p.Ala221=)

gnomAD frequency: 0.00424  dbSNP: rs147317366

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000340198	SCV000467109	benign	Batten-Turner congenital myopathy	2018-01-13	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.
GeneDx	RCV000422950	SCV000522675	benign	not specified	2016-03-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000532599	SCV000636340	benign	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form	2024-02-01	criteria provided, single submitter	clinical testing
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV000532599	SCV005038737	likely benign	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form		criteria provided, single submitter	research	The c.663G>A (p.(Ala221=)) variant was found in a heterozygous state in 2 Slovak patients with Myotonia congenita, both of whom carried 2 other Likely Pathogenic variants. It is a silent variant that has a population frequency not consistent with the disease (gnomAD ExomesVersion: 4.0 frequency f = 0.00515). Interestingly, both mentioned patients also carried heterozygous CLCN1 splicing variant c.2364+2T>C, indicating its inheritance in cis with c.663G>A.
CeGaT Center for Human Genetics Tuebingen	RCV004567870	SCV005051649	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	CLCN1: BP4, BP7, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV004567870	SCV005272693	benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004530447	SCV004730786	benign	CLCN1-related disorder	2020-04-27	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).