ClinVar Miner

Submissions for variant NM_001903.5(CTNNA1):c.1192A>G (p.Asn398Asp)

gnomAD frequency: 0.00003  dbSNP: rs773003463
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000801367 SCV000941141 uncertain significance not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 398 of the CTNNA1 protein (p.Asn398Asp). This variant is present in population databases (rs773003463, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CTNNA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 646977). 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 CTNNA1 protein function with a negative predictive value of 80%. 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.
GeneDx RCV000801367 SCV002588247 uncertain significance not provided 2022-04-27 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; Observed in multiple individuals who underwent multigene panel testing (Clark 2020); This variant is associated with the following publications: (PMID: 32051609)
Ambry Genetics RCV002336608 SCV002644112 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-23 criteria provided, single submitter clinical testing The p.N398D variant (also known as c.1192A>G), located in coding exon 8 of the CTNNA1 gene, results from an A to G substitution at nucleotide position 1192. The asparagine at codon 398 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Baylor Genetics RCV003472366 SCV004211275 uncertain significance Patterned macular dystrophy 2 2023-09-12 criteria provided, single submitter clinical testing

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