ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2645C>T (p.Pro882Leu)

gnomAD frequency: 0.00004  dbSNP: rs745329674
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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 RCV000991822 SCV001143595 uncertain significance not provided 2021-03-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001071809 SCV001237131 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 882 of the CLCN1 protein (p.Pro882Leu). This variant is present in population databases (rs745329674, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of 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: 804704). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV000991822 SCV001998271 uncertain significance not provided 2023-03-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD)
Revvity Omics, Revvity RCV000991822 SCV003830778 uncertain significance not provided 2019-07-19 criteria provided, single submitter clinical testing

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