ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1505+3A>G

gnomAD frequency: 0.00001  dbSNP: rs1227070716
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693110 SCV000820965 uncertain significance Tumor predisposition syndrome 3 2023-12-05 criteria provided, single submitter clinical testing This sequence change falls in intron 15 of the POT1 gene. It does not directly change the encoded amino acid sequence of the POT1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 571862). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV001011940 SCV001172324 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-14 criteria provided, single submitter clinical testing The c.1505+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 11 in the POT1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002510958 SCV002820339 uncertain significance not provided 2023-01-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge

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