Submissions for variant NM_000083.3(CLCN1):c.2180C>T (p.Pro727Leu)

gnomAD frequency: 0.39778  dbSNP: rs13438232

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000343234	SCV000467126	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	RCV000427667	SCV000519332	benign	not specified	2016-01-30	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	RCV001520613	SCV001729753	benign	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001579219	SCV001806672	benign	Congenital myotonia, autosomal dominant form	2021-07-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001579220	SCV001806673	benign	Congenital myotonia, autosomal recessive form	2021-07-22	criteria provided, single submitter	clinical testing
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV001520613	SCV005038725	likely benign	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form		criteria provided, single submitter	research	The c.2180C>T (p.(Pro727Leu)) variant was found in 20 Slovak patients with Myotonia congenita, in 4 and 16 of them in homozygous and heterozygous states, respectively. It is a silent variant, it is predicted to be benign by multiple in silico algorithms, and/or has a population frequency not consistent with the disease (gnomAD ExomesVersion: 4.0 frequency f = 0.408).
Breakthrough Genomics, Breakthrough Genomics	RCV004712365	SCV005272714	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000427667	SCV001740714	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000427667	SCV001955624	benign	not specified		no assertion criteria provided	clinical testing