ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8188G>A (p.Ala2730Thr)

dbSNP: rs1060503348
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004564117 SCV000552719 uncertain significance Familial adenomatous polyposis 1 2016-07-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 2730 of the APC protein (p.Ala2730Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002429545 SCV002680080 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-18 criteria provided, single submitter clinical testing The p.A2730T variant (also known as c.8188G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 8188. The alanine at codon 2730 is replaced by threonine, an amino acid with similar properties. This amino acid position is not 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.

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