ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3515A>T (p.His1172Leu)

gnomAD frequency: 0.00001  dbSNP: rs1024630299
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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 RCV003770253 SCV001388873 uncertain significance Familial adenomatous polyposis 1 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1172 of the APC protein (p.His1172Leu). This variant is not present in population databases (gnomAD no frequency). 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: 946225). 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.
Ambry Genetics RCV002451486 SCV002616388 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-22 criteria provided, single submitter clinical testing The p.H1172L variant (also known as c.3515A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 3515. The histidine at codon 1172 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002480716 SCV002793989 uncertain significance Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach 2022-05-23 criteria provided, single submitter clinical testing

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