ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.349C>T (p.Arg117Cys) (rs780936436)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000543907 SCV000655186 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 10 2017-05-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 117 of the POT1 protein (p.Arg117Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs780936436, ExAC 0.001%). This variant has been reported to segregate, in 3 families, with cardiac angiosarcoma and/or other cancer types associated with Li-fraumeni syndrome (PMID: 26403419). Experimental studies have shown that this missense change reduced POT1 binding to telomeres and increased telomere length and fragility (PMID: 26403419). In summary, this variant is a rare missense change shown to disrupt protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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