ClinVar Miner

Submissions for variant NM_013266.4(CTNNA3):c.999C>A (p.Asn333Lys)

gnomAD frequency: 0.00003  dbSNP: rs146754105
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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 RCV000474693 SCV000548888 uncertain significance Arrhythmogenic right ventricular dysplasia 13 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 333 of the CTNNA3 protein (p.Asn333Lys). This variant is present in population databases (rs146754105, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CTNNA3-related conditions. ClinVar contains an entry for this variant (Variation ID: 409010). 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 CTNNA3 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.
PreventionGenetics, part of Exact Sciences RCV003409628 SCV004114015 uncertain significance CTNNA3-related disorder 2022-12-17 criteria provided, single submitter clinical testing The CTNNA3 c.999C>A variant is predicted to result in the amino acid substitution p.Asn333Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.037% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-68940123-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004907646 SCV005568089 uncertain significance not specified 2024-11-25 criteria provided, single submitter clinical testing The c.999C>A (p.N333K) alteration is located in exon 7 (coding exon 6) of the CTNNA3 gene. This alteration results from a C to A substitution at nucleotide position 999, causing the asparagine (N) at amino acid position 333 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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