ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2260G>A (p.Val754Ile)

dbSNP: rs764099150
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216142 SCV000274237 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-11 criteria provided, single submitter clinical testing The p.V754I variant (also known as c.2260G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 2260. The valine at codon 754 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV004563155 SCV000768063 uncertain significance Familial adenomatous polyposis 1 2024-10-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 754 of the APC protein (p.Val754Ile). This variant is present in population databases (no rsID available, 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: 230625). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Sema4, Sema4 RCV000216142 SCV002528940 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-10 criteria provided, single submitter curation

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