ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.670G>A (p.Asp224Asn) (rs202187871)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000128427 SCV000655198 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 10 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 224 of the POT1 protein (p.Asp224Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs202187871, ExAC 0.007%). This variant has been observed to segregate with cutaneous malignant melanoma in one family (PMID: 24686846) and with Hodgkin lymphoma in another family (PMID:29693246). ClinVar contains an entry for this variant (Variation ID: 139527). Experimental studies have shown that this missense change disrupts POT1 from binding with the telomeric overhang in vitro and leads to telomere lengthening and fragility (PMID: 29693246). 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.
Ambry Genetics RCV000563340 SCV000674394 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
OMIM RCV000128427 SCV000172105 risk factor Melanoma, cutaneous malignant, susceptibility to, 10 2014-05-01 no assertion criteria provided literature only

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