ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2190G>A (p.Met730Ile)

dbSNP: rs1281171015
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773539 SCV000907233 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-06 criteria provided, single submitter clinical testing This missense variant replaces methionine with isoleucine at codon 730 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 1/250106 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.
Invitae RCV003534547 SCV000955678 uncertain significance Familial adenomatous polyposis 1 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 730 of the APC protein (p.Met730Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 559954). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284235 SCV001469903 uncertain significance not provided 2019-11-12 criteria provided, single submitter clinical testing
GeneDx RCV001284235 SCV002008113 uncertain significance not provided 2021-07-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528)
Ambry Genetics RCV000773539 SCV002724911 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-14 criteria provided, single submitter clinical testing The p.M730I variant (also known as c.2190G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 2190. The methionine at codon 730 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV002531388 SCV004207890 uncertain significance Familial adenomatous polyposis 1 2023-05-28 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677761 SCV000803917 uncertain significance Neoplasm of stomach 2017-08-26 no assertion criteria provided clinical testing

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