ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.107A>G (p.Tyr36Cys) (rs1057524691)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438630 SCV000536239 uncertain significance not provided 2018-04-05 criteria provided, single submitter clinical testing The Y36C variant in the POT1 gene has been reported previously in one family with chronic lymphocytic leukemia (Speedy et al., 2016). The Y36C variant is not observed in large population cohorts (Lek et al., 2016). The Y36C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This variant is located in the OB1 domain (Rice et al., 2017). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret Y36C as a variant of uncertain significance.
Invitae RCV000811957 SCV000952252 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 10 2018-11-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 36 of the POT1 protein (p.Tyr36Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with chronic lymphocytic leukemia (PMID: 27528712). ClinVar contains an entry for this variant (Variation ID: 392900). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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