ClinVar Miner

Submissions for variant NM_001830.4(CLCN4):c.1561G>A (p.Ala521Thr)

dbSNP: rs1924590136
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001332043 SCV001524241 uncertain significance Intellectual disability, X-linked 49 2020-04-05 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV005094421 SCV005797327 uncertain significance not provided 2024-07-20 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 521 of the CLCN4 protein (p.Ala521Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1030482). 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 CLCN4 protein function with a positive predictive value of 95%. 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.

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