NM_001142864.4(PIEZO1):c.5828G>A (p.Arg1943Gln) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Feb 1, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000880446.40

Allele description [Variation Report for NM_001142864.4(PIEZO1):c.5828G>A (p.Arg1943Gln)]

NM_001142864.4(PIEZO1):c.5828G>A (p.Arg1943Gln)

Gene:

PIEZO1:piezo type mechanosensitive ion channel component 1 (Er blood group) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_001142864.4(PIEZO1):c.5828G>A (p.Arg1943Gln)

HGVS:

NC_000016.10:g.88720506C>T
NG_042229.1:g.69715G>A
NM_001142864.4:c.5828G>AMANE SELECT
NP_001136336.2:p.Arg1943Gln
LRG_1137t1:c.5828G>A
LRG_1137:g.69715G>A
LRG_1137p1:p.Arg1943Gln
NC_000016.9:g.88786914C>T
NC_000016.9:g.88786914C>T
NM_001142864.2:c.5828G>A
NM_001142864.3:c.5828G>A
p.Arg1943Gln

Protein change:

R1943Q

Links:

dbSNP: rs115799619

NCBI 1000 Genomes Browser:

rs115799619

Molecular consequence:

NM_001142864.4:c.5828G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001023541	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 15, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001716280	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28716860, 30867417, 25741868
SCV001875081	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 20, 2021)	germline	clinical testing	Citation Link,
SCV002048148	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Likely benign (Aug 15, 2023)	germline	clinical testing	Citation Link,
SCV004138132	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Feb 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	33	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis.

Glogowska E, Schneider ER, Maksimova Y, Schulz VP, Lezon-Geyda K, Wu J, Radhakrishnan K, Keel SB, Mahoney D, Freidmann AM, Altura RA, Gracheva EO, Bagriantsev SN, Kalfa TA, Gallagher PG.

Blood. 2017 Oct 19;130(16):1845-1856. doi: 10.1182/blood-2017-05-786004. Epub 2017 Jul 17.

PubMed [citation]

PMID:: 28716860
PMCID:: PMC5649553

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001023541.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001716280.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	33	not provided	not provided	clinical testing	PubMed (3)

Description

BS2, BP4_strong, PS3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		33	not provided	not provided	not provided

From GeneDx, SCV001875081.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate gain-of-function: delayed return to normal of mechanically activated currents (Glogowska et al., 2017); This variant is associated with the following publications: (PMID: 32112123, 28716860, 29576450, 30867417, 28974772)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002048148.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004138132.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

PIEZO1: BP4, BS1, BS2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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