ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1765_1766del (p.Met589fs)

dbSNP: rs771968149
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000652228 SCV000774096 uncertain significance Tumor predisposition syndrome 3 2023-11-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met589Valfs*9) in the POT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the POT1 protein. This variant is present in population databases (rs771968149, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with thyroid cancer (PMID: 29625052). ClinVar contains an entry for this variant (Variation ID: 541882). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the C-terminus of the POT1 protein. Other variant(s) that disrupt this region (p.Asp617Glufs*9) have been observed in individuals with POT1-related conditions (PMID: 25482530). This suggests that this may be a clinically significant region of the protein. 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 RCV002397311 SCV002711768 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The c.1765_1766delAT variant, located in coding exon 14 of the POT1 gene, results from a deletion of two nucleotides at nucleotide positions 1765 to 1766, causing a translational frameshift with a predicted alternate stop codon (p.M589Vfs*9). This alteration occurs at the 3' terminus of thePOT1 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 46 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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