ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2260G>T (p.Val754Phe)

gnomAD frequency: 0.00001  dbSNP: rs764099150
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465815 SCV000552473 uncertain significance Familial adenomatous polyposis 1 2024-04-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 754 of the APC protein (p.Val754Phe). This variant is present in population databases (rs764099150, gnomAD 0.0009%). 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: 411352). 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.
Counsyl RCV000465815 SCV000785489 uncertain significance Familial adenomatous polyposis 1 2017-08-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002446834 SCV002737848 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-29 criteria provided, single submitter clinical testing The p.V754F variant (also known as c.2260G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 2260. The valine at codon 754 is replaced by phenylalanine, an amino acid with highly similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). 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.
Myriad Genetics, Inc. RCV000465815 SCV004018374 uncertain significance Familial adenomatous polyposis 1 2023-02-14 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV000465815 SCV004196400 uncertain significance Familial adenomatous polyposis 1 2024-03-04 criteria provided, single submitter clinical testing

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