ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1195A>G (p.Ile399Val)

dbSNP: rs2116462060
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001923640 SCV002196707 uncertain significance Tumor predisposition syndrome 3 2021-03-12 criteria provided, single submitter clinical testing 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. This sequence change replaces isoleucine with valine at codon 399 of the POT1 protein (p.Ile399Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies.
Ambry Genetics RCV004656737 SCV005150633 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-20 criteria provided, single submitter clinical testing The p.I399V variant (also known as c.1195A>G), located in coding exon 10 of the POT1 gene, results from an A to G substitution at nucleotide position 1195. The isoleucine at codon 399 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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