ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7471A>G (p.Met2491Val)

gnomAD frequency: 0.00008  dbSNP: rs375674083
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222149 SCV000275435 likely benign Hereditary cancer-predisposing syndrome 2021-03-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000232400 SCV000282822 uncertain significance Familial adenomatous polyposis 1 2022-10-14 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 2491 of the APC protein (p.Met2491Val). This variant is present in population databases (rs375674083, gnomAD 0.02%). This missense change has been observed in individual(s) with breast cancer and colorectal cancer (PMID: 28135145, 28503720). ClinVar contains an entry for this variant (Variation ID: 231549). 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. 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.
Counsyl RCV000232400 SCV000489391 uncertain significance Familial adenomatous polyposis 1 2016-10-03 criteria provided, single submitter clinical testing
Mendelics RCV000232400 SCV000838149 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758743 SCV000887553 uncertain significance not provided 2020-03-15 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000222149 SCV000909629 likely benign Hereditary cancer-predisposing syndrome 2023-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000758743 SCV001757938 uncertain significance not provided 2023-08-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast or colorectal cancer (Rummel et al., 2017; Yurgelun et al., 2017); This variant is associated with the following publications: (PMID: 28503720, 28135145)
Sema4, Sema4 RCV000222149 SCV002527668 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-14 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000232400 SCV004019634 uncertain significance Familial adenomatous polyposis 1 2023-02-15 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV000232400 SCV004196344 uncertain significance Familial adenomatous polyposis 1 2023-10-16 criteria provided, single submitter clinical testing

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