ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1064G>A (p.Gly355Glu)

gnomAD frequency: 0.00001  dbSNP: rs1282349760
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000711214 SCV000841546 likely pathogenic not provided 2017-12-19 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000711214 SCV002022571 likely pathogenic not provided 2021-03-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001861958 SCV002117703 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-08-09 criteria provided, single submitter clinical testing This sequence change affects codon 355 of the CLCN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CLCN1 protein. This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 18337100). ClinVar contains an entry for this variant (Variation ID: 585677). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
GeneDx RCV000711214 SCV002520176 likely pathogenic not provided 2022-05-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Exon-1 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; This variant is associated with the following publications: (PMID: 18337100, 17576681, 9536098)
MGZ Medical Genetics Center RCV002289993 SCV002579563 likely pathogenic Congenital myotonia, autosomal recessive form 2021-10-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001861958 SCV005667232 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-01-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.