ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.147del (p.Ile49fs) (rs1064794328)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485545 SCV000568855 likely pathogenic not provided 2017-01-25 criteria provided, single submitter clinical testing The c.147delT variant in the POT1 gene has been reported previously in association with an individual diagnosed with a glioma (Jones et al., 2015). The c.147delT variant causes a frameshift starting with codon Isoleucine 49, changes this amino acid to a Methionine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Ile49MetfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.147delT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.147delT as a likely pathogenic variant.
Invitae RCV000692016 SCV000819821 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 10 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile49Metfs*7) in the POT1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with glioma (PMID: 25877891). ClinVar contains an entry for this variant (Variation ID: 420174). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in POT1 cause disease. 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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