ClinVar Miner

Submissions for variant NM_000038.6(APC):c.10G>C (p.Ala4Pro)

dbSNP: rs774219012
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003766584 SCV000552662 uncertain significance Familial adenomatous polyposis 1 2023-09-15 criteria provided, single submitter clinical testing 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. This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 4 of the APC protein (p.Ala4Pro). This variant is present in population databases (rs774219012, gnomAD 0.006%). 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: 411481). 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 RCV001017299 SCV001178362 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-26 criteria provided, single submitter clinical testing The p.A4P variant (also known as c.10G>C), located in coding exon 1 of the APC gene, results from a G to C substitution at nucleotide position 10. The alanine at codon 4 is replaced by proline, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV001017299 SCV001353778 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-30 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 4 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 1/251352 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.
GeneDx RCV001753908 SCV002006771 uncertain significance not provided 2023-11-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV004001959 SCV004841680 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 4 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 1/251352 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.
3DMed Clinical Laboratory Inc RCV000677758 SCV000803914 uncertain significance Carcinoma of colon 2017-08-11 no assertion criteria provided clinical testing

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