ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1870A>G (p.Ile624Val)

gnomAD frequency: 0.00001  dbSNP: rs1410012081
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000546080 SCV000655169 uncertain significance Tumor predisposition syndrome 3 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 624 of the POT1 protein (p.Ile624Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myeloproliferative neoplasm (PMID: 34193977). ClinVar contains an entry for this variant (Variation ID: 475067). 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. 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 RCV001013412 SCV001173992 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-10 criteria provided, single submitter clinical testing The p.I624V variant (also known as c.1870A>G), located in coding exon 15 of the POT1 gene, results from an A to G substitution at nucleotide position 1870. The isoleucine at codon 624 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx RCV001764620 SCV001989020 uncertain significance not provided 2023-01-13 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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