ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.598G>A (p.Asp200Asn)

dbSNP: rs764943552
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687063 SCV000814614 uncertain significance Tumor predisposition syndrome 3 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 200 of the POT1 protein (p.Asp200Asn). This variant is present in population databases (rs764943552, 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: 567083). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV002352120 SCV002659714 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-09 criteria provided, single submitter clinical testing The p.D200N variant (also known as c.598G>A), located in coding exon 5 of the POT1 gene, results from a G to A substitution at nucleotide position 598. The aspartic acid at codon 200 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
GeneDx RCV002466563 SCV002762202 uncertain significance not provided 2022-06-08 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28393830)

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