ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5267C>T (p.Ser1756Phe)

gnomAD frequency: 0.00001  dbSNP: rs773178712
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569928 SCV000667546 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-20 criteria provided, single submitter clinical testing The p.S1756F variant (also known as c.5267C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 5267. The serine at codon 1756 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration was also detected on a 25-gene panel test in a Caucasian woman who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000569928 SCV001344202 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-09 criteria provided, single submitter clinical testing
Invitae RCV002232115 SCV001516231 uncertain significance Familial adenomatous polyposis 1 2023-07-12 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 482341). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs773178712, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1756 of the APC protein (p.Ser1756Phe).
GeneDx RCV001555805 SCV001777275 uncertain significance not provided 2019-12-20 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23873622)
Sema4, Sema4 RCV000569928 SCV002535142 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-16 criteria provided, single submitter curation
Baylor Genetics RCV003465214 SCV004207228 uncertain significance Familial adenomatous polyposis 1 2023-01-26 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677790 SCV000803946 uncertain significance Carcinoma of colon 2018-05-18 no assertion criteria provided clinical testing

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