Submissions for variant NM_000083.3(CLCN1):c.2023del (p.Gln675fs)

dbSNP: rs886042007

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000370138	SCV000330833	pathogenic	not provided	2016-09-23	criteria provided, single submitter	clinical testing	The c.2023delC pathogenic variant in the CLCN1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2023delC variant causes a frameshift starting with codon Glutamine 675, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 119 of the new reading frame, denoted p.Gln675LysfsX119. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2023delC variant was not observed in approximately 6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2023delC as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002519068	SCV003285282	pathogenic	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form	2022-01-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280880). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln675Lysfs*119) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125).