ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3314G>A (p.Arg1105Gln)

gnomAD frequency: 0.00001  dbSNP: rs548176472
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003650444 SCV000219118 uncertain significance Familial adenomatous polyposis 1 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1105 of the APC protein (p.Arg1105Gln). This variant is present in population databases (rs548176472, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of APC-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 188375). 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 RCV000567203 SCV000667454 likely benign Hereditary cancer-predisposing syndrome 2023-04-14 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 RCV000567203 SCV000681591 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-24 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 1105 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 APC-related disorders in the literature. This variant has been identified in 3/250386 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.
GeneDx RCV000998412 SCV002546690 uncertain significance not provided 2023-02-03 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27776115, 18199528)

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