Submissions for variant NM_001142864.4(PIEZO1):c.6307C>G (p.Leu2103Val)

gnomAD frequency: 0.00038  dbSNP: rs531972155

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000996381	SCV001151067	uncertain significance	not provided	2018-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000996381	SCV003271204	benign	not provided	2023-02-16	criteria provided, single submitter	clinical testing
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Southern Medical University	RCV004768770	SCV005374713	likely pathogenic	Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema	2024-10-16	criteria provided, single submitter	clinical testing	Disruption of PIEZO1 function can lead to Hereditary Xerocytosis. This sequence change replaces leucine with valine at codon 2103 of the PIEZO1 protein (p.Leu2103Val). This variant is a low-frequency mutation in population databases (1000Genomes: 0.00094), and the affected site is highly conserved across multiple species. This missense mutation was observed along with another PIEZO1 missense mutation (p.Gly46Ser) in a β-thalassemia carrier who exhibited symptoms resembling Hereditary Xerocytosis and presented with unusually severe anemia. Both SIFT and PolyPhen predict this to be a potentially pathogenic mutation. Structural modeling of the protein sequence and its biophysical properties suggests that this missense variant is likely to disrupt the function of the PIEZO1 protein. For these reasons, this variant has been classified as likely pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV000996381	SCV005412513	uncertain significance	not provided	2024-02-20	criteria provided, single submitter	clinical testing	BS2
PreventionGenetics, part of Exact Sciences	RCV003943303	SCV004759296	likely benign	PIEZO1-related disorder	2021-09-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).