ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1009A>G (p.Met337Val)

gnomAD frequency: 0.00001  dbSNP: rs1438780449
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589782 SCV000693985 uncertain significance not provided 2016-07-25 criteria provided, single submitter clinical testing Variant summary: The APC c.1009A>G (p.Met337Val) variant involves the alteration of a conserved nucleotide located at armadillo-type fold domain. 2/4 in silico tools predict a damaging outcome (SNPs&GO not captured due to low reliability index). This variant is absent in 121302 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is currently classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color Diagnostics, LLC DBA Color Health RCV000776695 SCV000912324 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-17 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 337 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 hereditary cancer in the literature. This variant has been identified in 1/31368 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 RCV003653215 SCV001236888 uncertain significance Familial adenomatous polyposis 1 2023-12-24 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 337 of the APC protein (p.Met337Val). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 495349). 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.
Ambry Genetics RCV000776695 SCV002739977 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-28 criteria provided, single submitter clinical testing The p.M337V variant (also known as c.1009A>G), located in coding exon 9 of the APC gene, results from an A to G substitution at nucleotide position 1009. The methionine at codon 337 is replaced by valine, 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.

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