Submissions for variant NM_000083.3(CLCN1):c.1096G>T (p.Val366Leu)

dbSNP: rs1554436573

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000517339	SCV000612752	uncertain significance	not specified	2017-01-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000811322	SCV000951582	uncertain significance	Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form	2022-03-29	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 366 of the CLCN1 protein (p.Val366Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myotonia congenita (Invitae). ClinVar contains an entry for this variant (Variation ID: 447044). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLCN1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000517339	SCV005422874	uncertain significance	not specified	2024-10-08	criteria provided, single submitter	clinical testing	Variant summary: CLCN1 c.1096G>T (p.Val366Leu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251482 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1096G>T in individuals affected with Congenital Myotonia, Autosomal Recessive Form and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 447044). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004737584	SCV005350797	uncertain significance	CLCN1-related disorder	2024-05-02	no assertion criteria provided	clinical testing	The CLCN1 c.1096G>T variant is predicted to result in the amino acid substitution p.Val366Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.