Submissions for variant NM_001142864.4(PIEZO1):c.7180G>A (p.Gly2394Ser)

gnomAD frequency: 0.00109  dbSNP: rs201950081

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mayo Clinic Laboratories, Mayo Clinic	RCV001508789	SCV001715162	uncertain significance	not provided	2023-05-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001508789	SCV001796639	uncertain significance	not provided	2023-02-21	criteria provided, single submitter	clinical testing	Observed in the heterozygous and homozygous states in multiple patients from a serology study, although clinical details were not provided (Karamatic et al. 2023); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 36122374, 32112123, 30187933, 29396846, 34201899)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001508789	SCV002047879	uncertain significance	not provided	2023-10-26	criteria provided, single submitter	clinical testing	The PIEZO1 c.7180G>A; p.Gly2394Ser variant (rs201950081) is reported in the literature in several individuals affected with dehydrated hereditary stomatocytosis, although its clinical significance was not demonstrated (Andolfo 2021, Russo 2018). This variant is found in the non-Finnish European population with an overall allele frequency of 0.20% (151/74762 alleles, including one homozygote) in the Genome Aggregation Database. The glycine at codon 2394 is weakly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.173). Due to limited and conflicting information, the clinical significance of the p.Gly2394Ser variant is uncertain at this time. References: Andolfo I et al. Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients. Genes (Basel). 2021 Jun 23;12(7):958. PMID: 34201899. Russo et al. Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias. Am J Hematol. 2018 May;93(5):672-682. PMID: 29396846.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001508789	SCV003226329	likely benign	not provided	2024-08-21	criteria provided, single submitter	clinical testing
OMIM	RCV003152631	SCV003841037	affects	Blood group, ER	2023-01-26	no assertion criteria provided	literature only
PreventionGenetics, part of Exact Sciences	RCV004740708	SCV005345303	uncertain significance	PIEZO1-related disorder	2024-05-09	no assertion criteria provided	clinical testing	The PIEZO1 c.7180G>A variant is predicted to result in the amino acid substitution p.Gly2394Ser. This variant was reported in an individual with dehydrated stomatocytosis; however, no additional evidence supported its pathogenicity (Russo et al. 2018. PubMed ID: 29396846). This variant is reported in 0.20% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.