Submissions for variant NM_001142864.4(PIEZO1):c.5289C>G (p.Tyr1763Ter)

dbSNP: rs72811487

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mayo Clinic Laboratories, Mayo Clinic	RCV001509530	SCV001716285	likely pathogenic	not provided	2020-07-21	criteria provided, single submitter	clinical testing	PVS1, PM2
Invitae	RCV001509530	SCV002246017	pathogenic	not provided	2021-07-01	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr1763*) in the PIEZO1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIEZO1 are known to be pathogenic (PMID: 26333996). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with colorectal adenomatous polyposis (PMID: 26780541). ClinVar contains an entry for this variant (Variation ID: 1163992). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.
Baylor Genetics	RCV003147633	SCV003834856	likely pathogenic	Lymphatic malformation 6	2021-05-31	criteria provided, single submitter	clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV003147633	SCV004048281	likely pathogenic	Lymphatic malformation 6		criteria provided, single submitter	clinical testing	The stop gained p.Y1763* in PIEZO1 (NM_001142864.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. The p.Y1763* variant is a loss of function variant in the gene PIEZO1, which is intolerant of Loss of Function variants. The variant has been submitted to ClinVar as Likely Pathogenic.The variant was identified in heterozygous state in one individual in a study where exome sequencing was performed to identify novel variants in unexplained adenomatous polyposis (Spier et al, 2016). For these reasons, this variant has been classified as Likely Pathogenic. The observed variant was also detected in the spouse.
GeneDx	RCV001509530	SCV004169240	pathogenic	not provided	2023-11-03	criteria provided, single submitter	clinical testing	Has not been previously reported as a pathogenic or benign variant in association with PIEZO1-related lymphatic malformation or PIEZO1-related dehydrated hereditary stomatocytosis; however, was observed in an individual with a particular red blood cell antigen described as Er(a-b-) red blood cell phenotype who also possessed a second missense PIEZO variant (Karamatic Crew et al., 2023); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26780541, 34358671, 36122374)
OMIM	RCV003152634	SCV003841039	pathogenic	ER BLOOD GROUP SYSTEM, ER(a-b-)	2023-01-26	no assertion criteria provided	literature only