ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3229G>C (p.Val1077Leu)

gnomAD frequency: 0.00001  dbSNP: rs1332655563
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569426 SCV000672561 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-13 criteria provided, single submitter clinical testing The p.V1077L variant (also known as c.3229G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 3229. The valine at codon 1077 is replaced by leucine, an amino acid with highly similar properties. 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.
Invitae RCV003537187 SCV000824811 uncertain significance Familial adenomatous polyposis 1 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1077 of the APC protein (p.Val1077Leu). 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: 485123). 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.
Color Diagnostics, LLC DBA Color Health RCV000569426 SCV001348365 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces valine with leucine at codon 1077 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
Mendelics RCV002248788 SCV002516879 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000569426 SCV002533170 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-29 criteria provided, single submitter curation

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