ClinVar Miner

Submissions for variant NM_001142864.4(PIEZO1):c.6058G>A (p.Ala2020Thr)

dbSNP: rs587776989
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224939 SCV000281314 pathogenic not provided 2016-02-19 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000224939 SCV001716277 likely pathogenic not provided 2021-03-10 criteria provided, single submitter clinical testing PM2, PS3, PP1_moderate
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000224939 SCV004026675 pathogenic not provided 2023-08-15 criteria provided, single submitter clinical testing
GeneDx RCV000224939 SCV005628329 pathogenic not provided 2024-07-17 criteria provided, single submitter clinical testing Published functional studies demonstrate an increase in the inactivation time compared to wild type channel kinetics, indicating that variant results in a gain-of-function (PMID: 23695678); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29952828, 29449963, 28971506, 33181827, 9827909, 23695678, 17253968)
Labcorp Genetics (formerly Invitae), Labcorp RCV000224939 SCV005838449 pathogenic not provided 2024-06-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2020 of the PIEZO1 protein (p.Ala2020Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with dehydrated hereditary stomatocytosis (PMID: 23695678, 29952828). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 55807). 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 expected to disrupt PIEZO1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000049233 SCV000077486 pathogenic Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema 2013-01-01 no assertion criteria provided literature only

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