ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1610G>A (p.Ser537Asn)

gnomAD frequency: 0.00001  dbSNP: rs1001526630
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491020 SCV000579864 uncertain significance Hereditary cancer-predisposing syndrome 2025-02-14 criteria provided, single submitter clinical testing The p.S537N variant (also known as c.1610G>A), located in coding exon 12 of the APC gene, results from a G to A substitution at nucleotide position 1610. The serine at codon 537 is replaced by asparagine, an amino acid with highly similar properties. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000646265 SCV000768033 uncertain significance Familial adenomatous polyposis 1 2024-11-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 537 of the APC protein (p.Ser537Asn). This variant is present in population databases (no rsID available, gnomAD 0.008%). This missense change has been observed in individual(s) with breast cancer (PMID: 33646313). ClinVar contains an entry for this variant (Variation ID: 428134). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV000646265 SCV000838080 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000646265 SCV003843031 uncertain significance Familial adenomatous polyposis 1 2022-01-06 criteria provided, single submitter clinical testing The APC c.1610G>A (p.Ser537Asn) missense change has a maximum subpopulation frequency of 0.0080% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with APC-related familial adenomatous polyposis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. 
Color Diagnostics, LLC DBA Color Health RCV000491020 SCV004362607 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-11 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 537 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 2/282118 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.
All of Us Research Program, National Institutes of Health RCV004003443 SCV004837424 uncertain significance Classic or attenuated familial adenomatous polyposis 2023-11-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV000646265 SCV005054081 uncertain significance Familial adenomatous polyposis 1 2023-11-07 criteria provided, single submitter clinical testing

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