ClinVar Miner

Submissions for variant NM_000038.6(APC):c.280C>A (p.Arg94Ser)

gnomAD frequency: 0.00002  dbSNP: rs550945533
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409081 SCV000487983 uncertain significance Familial adenomatous polyposis 1 2015-12-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000409081 SCV000947813 uncertain significance Familial adenomatous polyposis 1 2023-09-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 94 of the APC protein (p.Arg94Ser). This variant is present in population databases (rs550945533, 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: 371803). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV001016652 SCV001177628 likely benign Hereditary cancer-predisposing syndrome 2023-03-16 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.
GeneDx RCV001775785 SCV002013247 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153569 SCV003843477 benign Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000409081 SCV004018230 uncertain significance Familial adenomatous polyposis 1 2023-02-14 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 RCV000409081 SCV004207428 uncertain significance Familial adenomatous polyposis 1 2022-09-19 criteria provided, single submitter clinical testing

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