ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5213A>C (p.His1738Pro)

dbSNP: rs149882057
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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 RCV003765049 SCV000218736 benign Familial adenomatous polyposis 1 2024-12-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001182080 SCV001347427 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV001182080 SCV002640584 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-03 criteria provided, single submitter clinical testing The p.H1738P variant (also known as c.5213A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 5213. The histidine at codon 1738 is replaced by proline, an amino acid with similar properties. This variant has been identified in 7/12503 unselected Japanese colorectal cancer patients and in 6/23705 controls (Fujita M et al. Clin Gastroenterol Hepatol, 2022 Sep;20:2132-2141.e9). 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.
All of Us Research Program, National Institutes of Health RCV004804779 SCV005424833 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces histidine with proline at codon 1738 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a case-control study, this variant was identified in 7/12501 colorectal cancer cases & 6/23705 controls (PMID: 33309985). This variant has been observed as homozgyous in an individual affected with familial adenomatous polyposis (FAP) who also had multiplex ligation-dependent probe amplification testing showing a large heterozygous deletion of the APC gene (PMID: 35189564). This variant has been identified in 1/250664 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.

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