ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7382C>T (p.Ser2461Leu)

dbSNP: rs1413542387
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002556448 SCV002189216 uncertain significance Familial adenomatous polyposis 1 2024-07-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2461 of the APC protein (p.Ser2461Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1417979). 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 APC protein function with a negative 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.
PreventionGenetics, part of Exact Sciences RCV004728938 SCV005337971 uncertain significance APC-related disorder 2024-07-16 no assertion criteria provided clinical testing The APC c.7382C>T variant is predicted to result in the amino acid substitution p.Ser2461Leu. This variant has been reported as somatic in one individual with malignant melanoma (Table S1 and S2. Van Allen et al. 2015. PubMed ID: 26359337) but has not been reported as germline in any individuals with APC-related conditions. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD and is classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1417979/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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