ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1441G>A (p.Glu481Lys) (rs200494750)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562465 SCV000674411 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000652213 SCV000774081 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 10 2018-10-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 481 of the POT1 protein (p.Glu481Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs200494750, ExAC 0.01%). This variant has not been reported in the literature in individuals with POT1-related disease. ClinVar contains an entry for this variant (Variation ID: 486141). 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. 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.

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