ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2545G>A (p.Ala849Thr)

gnomAD frequency: 0.00030  dbSNP: rs201861334
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000368010 SCV000467132 likely benign Batten-Turner congenital myopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000700433 SCV000829187 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 849 of the CLCN1 protein (p.Ala849Thr). This variant is present in population databases (rs201861334, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with clinical features of CLCN1-related conditions (PMID: 31216405). ClinVar contains an entry for this variant (Variation ID: 359124). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Athena Diagnostics Inc RCV000711230 SCV000841562 uncertain significance not provided 2022-08-18 criteria provided, single submitter clinical testing
Baylor Genetics RCV000700433 SCV000992750 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2012-10-17 criteria provided, single submitter clinical testing
GeneDx RCV000711230 SCV001803633 uncertain significance not provided 2022-09-28 criteria provided, single submitter clinical testing Previously reported as a variant of uncertain significance in the heterozygous state in a patient with Schinzel-Giedion syndrome who also harbored a de novo SETBP1 pathogenic variant (Volk et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25852444, 31216405)
Revvity Omics, Revvity RCV000711230 SCV003830758 uncertain significance not provided 2023-02-27 criteria provided, single submitter clinical testing

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