Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000795520 | SCV000934985 | uncertain significance | Tumor predisposition syndrome 3 | 2022-07-11 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 150 of the POT1 protein (p.Leu150Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 642122). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV001022585 | SCV001184339 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-16 | criteria provided, single submitter | clinical testing | The p.L150S variant (also known as c.449T>C), located in coding exon 4 of the POT1 gene, results from a T to C substitution at nucleotide position 449. The leucine at codon 150 is replaced by serine, an amino acid with dissimilar properties. This variant was described as a germline finding in 1/3323 consecutive patients who had clinical testing for variants associated with hematologic malignancies (Lim TL et al. Leukemia, 2022 Jan;36:283-287). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV002509540 | SCV002818803 | uncertain significance | not provided | 2023-01-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) (Lim et al., 2021); This variant is associated with the following publications: (PMID: 34193977) |