ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7264A>T (p.Thr2422Ser)

dbSNP: rs730881260
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575939 SCV000672525 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-16 criteria provided, single submitter clinical testing The p.T2422S variant (also known as c.7264A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 7264. The threonine at codon 2422 is replaced by serine, an amino acid with similar properties. In one study, this variant was detected in 1/1324 individuals with colorectal cancer and 0/93 controls (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003471900 SCV000768261 uncertain significance Familial adenomatous polyposis 1 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2422 of the APC protein (p.Thr2422Ser). This variant is present in population databases (rs730881260, gnomAD 0.002%). 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: 485104). 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.
Color Diagnostics, LLC DBA Color Health RCV000575939 SCV001736304 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-10 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 2422 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 2/250322 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001755953 SCV002006023 uncertain significance not provided 2020-02-12 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Baylor Genetics RCV003471900 SCV004200787 uncertain significance Familial adenomatous polyposis 1 2023-08-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001097 SCV004843525 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 2422 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 2/250322 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV005034138 SCV005667888 uncertain significance Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach 2024-06-13 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000582754 SCV000691764 uncertain significance not specified no assertion criteria provided clinical testing

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