ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2798C>A (p.Ser933Tyr)

dbSNP: rs1448219970
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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 RCV000812692 SCV000953014 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 933 of the CLCN1 protein (p.Ser933Tyr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 656306). 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 with a negative predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002538127 SCV003674042 uncertain significance Inborn genetic diseases 2022-12-06 criteria provided, single submitter clinical testing The c.2798C>A (p.S933Y) alteration is located in exon 23 (coding exon 23) of the CLCN1 gene. This alteration results from a C to A substitution at nucleotide position 2798, causing the serine (S) at amino acid position 933 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003145174 SCV003830683 uncertain significance not provided 2019-10-11 criteria provided, single submitter clinical testing

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