Submissions for variant NM_000083.3(CLCN1):c.775C>T (p.Gln259Ter)

dbSNP: rs2116842799

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001934760	SCV002136144	pathogenic	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form	2022-04-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln259*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV004527434	SCV005038738	likely pathogenic	Congenital myotonia, autosomal recessive form		criteria provided, single submitter	research	The c.775C>T (p.(Gln259*)) variant was found in a homozygous state in 1 Slovak patient with Myotonia congenita. It leads to a premature stop codon and has not been reported in the public part of the HGMD or gnomAD Exomes databases. No other Pathogenic or Likely pathogenic variants were found in this individual.