Submissions for variant NM_001142864.4(PIEZO1):c.6584C>T (p.Ser2195Leu)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV003142669	SCV003813016	uncertain significance	not provided	2022-08-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003142669	SCV004521224	benign	not provided	2022-11-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004741458	SCV005349194	uncertain significance	PIEZO1-related disorder	2024-08-16	no assertion criteria provided	clinical testing	The PIEZO1 c.6584C>T variant is predicted to result in the amino acid substitution p.Ser2195Leu. This variant has been reported in the compound heterozygous state in an individual with fetal lethality (Table 3, Najafi et al. 2021. PubMed ID: 33772059) and was also reported compound heterozygous in an individual with prune belly syndrome (Amado et al. 2024. PubMed ID: 38184690). A functional study using HEK293T cells shows that this variant affects channel gaiting and decreased sensitivity to pressure changes (Amado et al. 2024. PubMed ID: 38184690). This variant is reported in 0.018% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.