NM_001142864.4(PIEZO1):c.6019A>C (p.Met2007Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 20, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003727164.2

Allele description [Variation Report for NM_001142864.4(PIEZO1):c.6019A>C (p.Met2007Leu)]

NM_001142864.4(PIEZO1):c.6019A>C (p.Met2007Leu)

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.6019A>C (p.Met2007Leu)

HGVS:

NC_000016.10:g.88720214T>G
NG_042229.1:g.70007A>C
NM_001142864.4:c.6019A>CMANE SELECT
NM_014745.1:c.4561A>C
NP_001136336.2:p.Met2007Leu
NP_055560.1:p.Met1521Leu
LRG_1137t1:c.6019A>C
LRG_1137:g.70007A>C
LRG_1137p1:p.Met2007Leu
NC_000016.9:g.88786622T>G

Protein change:

M1521L

Molecular consequence:

NM_001142864.4:c.6019A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014745.1:c.4561A>C - 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
SCV004535595	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30655378, 32109669, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004535595

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 20, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

Clinical and biological features in PIEZO1-hereditary xerocytosis and Gardos channelopathy: a retrospective series of 126 patients.

Picard V, Guitton C, Thuret I, Rose C, Bendelac L, Ghazal K, Aguilar-Martinez P, Badens C, Barro C, Bénéteau C, Berger C, Cathébras P, Deconinck E, Delaunay J, Durand JM, Firah N, Galactéros F, Godeau B, Jaïs X, de Jaureguiberry JP, Le Stradic C, Lifermann F, et al.

Haematologica. 2019 Aug;104(8):1554-1564. doi: 10.3324/haematol.2018.205328. Epub 2019 Jan 17.

PubMed [citation]

PMID:: 30655378
PMCID:: PMC6669138

Heterogeneous phenotype of Hereditary Xerocytosis in association with PIEZO1 variants.

de Meira Oliveira P, Balan A, Muto NH, Cervato MC, Fonseca GHH, Suganuma LM, Gualandro S, Pinho JRR, Mohandas N, Silveira PAA, Sitnik R.

Blood Cells Mol Dis. 2020 May;82:102413. doi: 10.1016/j.bcmd.2020.102413. Epub 2020 Feb 8.

PubMed [citation]

PMID:: 32109669

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004535595.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PIEZO1 protein function. This missense change has been observed in individuals with autosomal dominant hereditary xerocytosis (PMID: 30655378, 32109669). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2007 of the PIEZO1 protein (p.Met2007Leu).

#	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

Last Updated: Sep 29, 2024

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