NM_001142864.4(PIEZO1):c.4666C>T (p.Gln1556Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 21, 2022
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:: RCV002824058.2

Allele description [Variation Report for NM_001142864.4(PIEZO1):c.4666C>T (p.Gln1556Ter)]

NM_001142864.4(PIEZO1):c.4666C>T (p.Gln1556Ter)

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.4666C>T (p.Gln1556Ter)

HGVS:

NC_000016.10:g.88722839G>A
NG_042229.1:g.67382C>T
NM_001142864.4:c.4666C>TMANE SELECT
NM_014745.1:c.3208C>T
NP_001136336.2:p.Gln1556Ter
NP_055560.1:p.Gln1070Ter
LRG_1137t1:c.4666C>T
LRG_1137:g.67382C>T
LRG_1137p1:p.Gln1556Ter
NC_000016.9:g.88789247G>A

Protein change:

Q1070*

Molecular consequence:

NM_001142864.4:c.4666C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014745.1:c.3208C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003201071	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26333996, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003201071

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 21, 2022)

germline

clinical testing

PubMed (2)
[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

Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis.

Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G, Atton G, Jeffery I, Rees DC, Mignot C, Vogt J, Homfray T, Snyder MP, Rockson SG, Jeffery S, Mortimer PS, Mansour S, Ostergaard P.

Nat Commun. 2015 Sep 3;6:8085. doi: 10.1038/ncomms9085. Erratum in: Nat Commun. 2019 Apr 26;10(1):1951. doi: 10.1038/s41467-019-09905-4.

PubMed [citation]

PMID:: 26333996
PMCID:: PMC4568316

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

Details of each submission

From Invitae, SCV003201071.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with PIEZO1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1556*) 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).

#	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: Feb 20, 2024

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