ClinVar Miner

Submissions for variant NM_001903.5(CTNNA1):c.293G>A (p.Arg98Gln)

gnomAD frequency: 0.00008  dbSNP: rs746832628
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000791893 SCV000931160 uncertain significance not provided 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 98 of the CTNNA1 protein (p.Arg98Gln). This variant is present in population databases (rs746832628, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). ClinVar contains an entry for this variant (Variation ID: 639160). 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.
Ambry Genetics RCV001017615 SCV001178718 benign Hereditary cancer-predisposing syndrome 2023-02-25 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV003392597 SCV004119106 uncertain significance CTNNA1-related disorder 2022-10-05 criteria provided, single submitter clinical testing The CTNNA1 c.293G>A variant is predicted to result in the amino acid substitution p.Arg98Gln. This variant was reported as a variant of uncertain significance in a study of gastric or breast cancer (Clark et al 2020. PubMed ID: 32051609). This variant is reported in 0.049% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-138119053-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003472332 SCV004211252 uncertain significance Patterned macular dystrophy 2 2023-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000791893 SCV005325748 uncertain significance not provided 2023-05-31 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals referred for hereditary cancer multi-gene panel testing (Clark et al., 2020); This variant is associated with the following publications: (PMID: Molina2021[Poster], 32051609)

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