ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1399A>G (p.Lys467Glu)

gnomAD frequency: 0.00001  dbSNP: rs149892539
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000711218 SCV000841550 likely pathogenic not provided 2023-10-27 criteria provided, single submitter clinical testing This variant has been identified in at least one individual with clinical features associated with this gene. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) Computational tools yielded predictions that this variant may interfere with normal RNA splicing. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001063068 SCV001227902 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 467 of the CLCN1 protein (p.Lys467Glu). This variant is present in population databases (rs149892539, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive CLCN1-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 585680). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000711218 SCV001771997 uncertain significance not provided 2020-12-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant does not alter protein structure/function
Revvity Omics, Revvity RCV000711218 SCV003832357 uncertain significance not provided 2021-09-01 criteria provided, single submitter clinical testing

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