Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002037678 | SCV002233582 | pathogenic | Tumor predisposition syndrome 3 | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn441Lysfs*2) in the POT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POT1 are known to be pathogenic (PMID: 32155570). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 1452522). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002386815 | SCV002688998 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-29 | criteria provided, single submitter | clinical testing | The c.1322dupA variant, located in coding exon 10 of the POT1 gene, results from a duplication of A at nucleotide position 1322, causing a translational frameshift with a predicted alternate stop codon (p.N441Kfs*2). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Clinical Genomics Laboratory, |
RCV002037678 | SCV005045154 | likely pathogenic | Tumor predisposition syndrome 3 | 2023-12-26 | criteria provided, single submitter | clinical testing | The POT1 c.1322dup (p.Asn441LysfsTer2) variant, to our knowledge, has not been reported in the medical literature. This variant is only observed on 1/250,876 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by inserting a single nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Loss-of-function variants in POT1 are known to be pathogenic (Gong Y et al., PMID: 32155570). This variant has been reported in the ClinVar database as a pathogenic germline variant by two submitters. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic. |