ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1925T>C (p.Val642Ala)

gnomAD frequency: 0.00001  dbSNP: rs759528091
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506828 SCV000600051 uncertain significance not specified 2017-04-28 criteria provided, single submitter clinical testing
Invitae RCV003535798 SCV000768167 uncertain significance Familial adenomatous polyposis 1 2022-09-12 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: 438869). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs759528091, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 642 of the APC protein (p.Val642Ala).
Mendelics RCV000646398 SCV000838085 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001188846 SCV001355992 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces valine with alanine at codon 642 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. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 2/251214 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.
Ambry Genetics RCV001188846 SCV002720683 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-30 criteria provided, single submitter clinical testing The p.V642A variant (also known as c.1925T>C), located in coding exon 14 of the APC gene, results from a T to C substitution at nucleotide position 1925. The valine at codon 642 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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