ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4594G>A (p.Asp1532Asn)

gnomAD frequency: 0.00001  dbSNP: rs730881251
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159556 SCV000209527 uncertain significance not provided 2019-08-26 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Illumina Laboratory Services, Illumina RCV000291608 SCV000452014 uncertain significance APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563203 SCV000667548 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-16 criteria provided, single submitter clinical testing The p.D1532N variant (also known as c.4594G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 4594. The aspartic acid at codon 1532 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003534409 SCV000950867 uncertain significance Familial adenomatous polyposis 1 2023-10-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1532 of the APC protein (p.Asp1532Asn). This variant is present in population databases (rs730881251, gnomAD 0.002%). 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: 181807). 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.
Mendelics RCV000810645 SCV001136916 uncertain significance Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000563203 SCV001347426 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-11 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 1532 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with ovarian cancer (DOI: 10.1101/2021.04.15.21255554). This variant has been identified in 2/250372 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159556 SCV001469306 uncertain significance not provided 2019-10-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002509260 SCV002819422 uncertain significance not specified 2022-12-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV000810645 SCV004198758 uncertain significance Familial adenomatous polyposis 1 2023-10-15 criteria provided, single submitter clinical testing

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