ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3638C>T (p.Ser1213Leu)

dbSNP: rs1554085199
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003538443 SCV000768092 uncertain significance Familial adenomatous polyposis 1 2023-06-20 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1213 of the APC protein (p.Ser1213Leu). This variant is not present in population databases (gnomAD no frequency). 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: 537453). 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. 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.
Color Diagnostics, LLC DBA Color Health RCV001187685 SCV001354551 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-14 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 1213 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). 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.
Ambry Genetics RCV001187685 SCV002614191 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-13 criteria provided, single submitter clinical testing The p.S1213L variant (also known as c.3638C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3638. The serine at codon 1213 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not 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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