ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1301A>T (p.Asp434Val)

dbSNP: rs1762873545
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003649283 SCV001202946 uncertain significance Familial adenomatous polyposis 1 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 434 of the APC protein (p.Asp434Val). 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: 837969). 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%. Studies have shown that this missense change is associated with inconclusive levels of altered splicing (Invitae). 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 RCV002379494 SCV002689851 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-06 criteria provided, single submitter clinical testing The p.D434V variant (also known as c.1301A>T), located in coding exon 9 of the APC gene, results from an A to T substitution at nucleotide position 1301. The aspartic acid at codon 434 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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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