ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.419C>A (p.Ala140Asp)

dbSNP: rs1435631505
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001366421 SCV001562722 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2020-08-14 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with CLCN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 140 of the CLCN1 protein (p.Ala140Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid.
GeneDx RCV002284486 SCV002574512 uncertain significance not provided 2022-03-18 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; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003284276 SCV003968166 uncertain significance Inborn genetic diseases 2023-04-18 criteria provided, single submitter clinical testing The c.419C>A (p.A140D) alteration is located in exon 3 (coding exon 3) of the CLCN1 gene. This alteration results from a C to A substitution at nucleotide position 419, causing the alanine (A) at amino acid position 140 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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