ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7148G>T (p.Gly2383Val)

dbSNP: rs754320004
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568737 SCV000667695 likely benign Hereditary cancer-predisposing syndrome 2022-08-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Color Diagnostics, LLC DBA Color Health RCV000568737 SCV000681850 uncertain significance Hereditary cancer-predisposing syndrome 2021-01-12 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 2383 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 familial adenomatous polyposis in the literature. This variant has been identified in 2/250230 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 RCV003459338 SCV000768289 uncertain significance Familial adenomatous polyposis 1 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2383 of the APC protein (p.Gly2383Val). This variant is present in population databases (rs754320004, gnomAD 0.01%). 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: 482440). 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.
Baylor Genetics RCV003459338 SCV004199454 uncertain significance Familial adenomatous polyposis 1 2023-10-09 criteria provided, single submitter clinical testing

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