ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2024A>C (p.Gln675Pro)

gnomAD frequency: 0.00005  dbSNP: rs768582911
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000516361 SCV000612774 uncertain significance not specified 2016-08-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000815375 SCV000955825 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 675 of the CLCN1 protein (p.Gln675Pro). This variant is present in population databases (rs768582911, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 447059). 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 not 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.
Revvity Omics, Revvity RCV003144302 SCV003830770 uncertain significance not provided 2021-10-12 criteria provided, single submitter clinical testing
GeneDx RCV003144302 SCV005079844 uncertain significance not provided 2024-01-03 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 RCV004609418 SCV005103603 uncertain significance Inborn genetic diseases 2024-03-31 criteria provided, single submitter clinical testing The c.2024A>C (p.Q675P) alteration is located in exon 17 (coding exon 17) of the CLCN1 gene. This alteration results from a A to C substitution at nucleotide position 2024, causing the glutamine (Q) at amino acid position 675 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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