ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1972_1973delinsAT (p.Glu658Met)

dbSNP: rs1765077325
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003649353 SCV001223017 uncertain significance Familial adenomatous polyposis 1 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with methionine, which is neutral and non-polar, at codon 658 of the APC protein (p.Glu658Met). This variant is present in population databases (no rsID available, gnomAD 0.0004%). 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: 853601). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV001190023 SCV001357434 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with methionine at codon 658 of the APC protein. 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 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.
Ambry Genetics RCV001190023 SCV002721619 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-15 criteria provided, single submitter clinical testing The c.1972_1973delGAinsAT variant, located in coding exon 15 of the APC gene, results from an in-frame deletion of GA and insertion of AT at nucleotide positions 1972 to 1973. This results in the substitution of the glutamic acid residue for a methionine residue at codon 658, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003442181 SCV004169066 uncertain significance not provided 2023-11-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533, 18199528)

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