ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2573T>G (p.Ile858Ser)

dbSNP: rs1765215022
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001189315 SCV001356580 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-06 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with serine at codon 858 of the APC protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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 RCV002280164 SCV002568458 uncertain significance not provided 2022-02-23 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
Ambry Genetics RCV001189315 SCV004001070 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-22 criteria provided, single submitter clinical testing The p.I858S variant (also known as c.2573T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 2573. The isoleucine at codon 858 is replaced by serine, an amino acid with dissimilar 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.

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