NM_001142864.4(PIEZO1):c.1591C>T (p.Arg531Cys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Nov 23, 2022
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:: RCV001811589.20

Allele description [Variation Report for NM_001142864.4(PIEZO1):c.1591C>T (p.Arg531Cys)]

NM_001142864.4(PIEZO1):c.1591C>T (p.Arg531Cys)

Genes:

HSALR1:HSP90AB1 associated lncRNA 1 [Gene - HGNC]
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.1591C>T (p.Arg531Cys)

HGVS:

NC_000016.10:g.88735213G>A
NG_042229.1:g.55008C>T
NM_001142864.4:c.1591C>TMANE SELECT
NP_001136336.2:p.Arg531Cys
LRG_1137t1:c.1591C>T
LRG_1137:g.55008C>T
LRG_1137p1:p.Arg531Cys
NC_000016.9:g.88801621G>A
NM_001142864.2:c.1591C>T
NM_001142864.3:c.1591C>T

Protein change:

R531C

Links:

dbSNP: rs146505418

NCBI 1000 Genomes Browser:

rs146505418

Molecular consequence:

NM_001142864.4:c.1591C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001158295	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (May 25, 2021)	germline	clinical testing	Citation Link,
SCV002552786	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 28, 2022)	germline	clinical testing	Citation Link,
SCV003265338	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Sep 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003812991	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005193289	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158295.3

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

Description

The PIEZO1 c.1591C>T; p.Arg531Cys variant (rs146505418), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the general population with an overall allele frequency of 0.047 % (89 / 187,772 alleles) in the Genome Aggregation Database. The arginine at codon 531 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Arg531Cys variant is uncertain at this time.

#	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 GeneDx, SCV002552786.2

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003265338.2

#	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 Revvity Omics, Revvity, SCV003812991.2

#	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 Breakthrough Genomics, Breakthrough Genomics, SCV005193289.1

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

#	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

Last Updated: Nov 3, 2024

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