ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.809G>A (p.Ser270Asn)

dbSNP: rs587777477
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000128425 SCV001586052 pathogenic Tumor predisposition syndrome 3 2023-05-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects POT1 function (PMID: 24686846, 27869160). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POT1 protein function. ClinVar contains an entry for this variant (Variation ID: 139525). This missense change has been observed in individual(s) with melanoma (PMID: 24686846). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 270 of the POT1 protein (p.Ser270Asn).
Sema4, Sema4 RCV002256085 SCV002527176 pathogenic Hereditary cancer-predisposing syndrome 2021-10-14 criteria provided, single submitter curation
Ambry Genetics RCV002256085 SCV002679115 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-19 criteria provided, single submitter clinical testing The p.S270N variant (also known as c.809G>A), located in coding exon 6 of the POT1 gene, results from a G to A substitution at nucleotide position 809. The serine at codon 270 is replaced by asparagine, an amino acid with highly similar properties. This variant was identified in 1/167 Italian individuals with cutaneous melanoma who were CDKN2A/ARF- and CDK4-negative (Pastorino L et al. Cancers (Basel), 2020 04;12:). This variant was also identified in five unrelated melanoma-prone families from Romagna, Italy and described as a founder mutation (Shi J et al. Nat Genet, 2014 May;46:482-6). 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. Based on the available evidence, the clinical significance of this variant remains unclear.
OMIM RCV000128425 SCV000172103 pathogenic Tumor predisposition syndrome 3 2014-05-01 no assertion criteria provided literature only
GeneReviews RCV000128425 SCV001478028 not provided Tumor predisposition syndrome 3 no assertion provided literature only Founder variant in Romagna region of Italy

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.