ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5290C>G (p.Gln1764Glu)

gnomAD frequency: 0.00002  dbSNP: rs529543591
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129346 SCV000184110 benign Hereditary cancer-predisposing syndrome 2022-07-14 criteria provided, single submitter clinical testing This alteration is classified as 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000206391 SCV000260053 uncertain significance Familial adenomatous polyposis 1 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1764 of the APC protein (p.Gln1764Glu). This variant is present in population databases (rs529543591, gnomAD 0.02%). 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: 141021). 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.
Counsyl RCV000206391 SCV000489347 uncertain significance Familial adenomatous polyposis 1 2016-09-26 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000129346 SCV000681728 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-07 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 1764 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 5/250532 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.
Myriad Genetics, Inc. RCV000206391 SCV004018782 uncertain significance Familial adenomatous polyposis 1 2023-02-21 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 RCV000206391 SCV004201366 uncertain significance Familial adenomatous polyposis 1 2023-08-25 criteria provided, single submitter clinical testing
GeneDx RCV004589623 SCV005078538 uncertain significance not provided 2023-10-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer (Chen et al., 2020); This variant is associated with the following publications: (PMID: 32091409, 18199528)
3DMed Clinical Laboratory Inc RCV000677788 SCV000803944 uncertain significance Colorectal cancer 2018-05-21 no assertion criteria provided clinical testing

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