NM_001126108.2(SLC12A3):c.1805_1806del (p.Tyr602fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 10, 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:: RCV001386501.7

Allele description [Variation Report for NM_001126108.2(SLC12A3):c.1805_1806del (p.Tyr602fs)]

NM_001126108.2(SLC12A3):c.1805_1806del (p.Tyr602fs)

Gene:

SLC12A3:solute carrier family 12 member 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q13

Genomic location:

Preferred name:

NM_001126108.2(SLC12A3):c.1805_1806del (p.Tyr602fs)

HGVS:

NC_000016.10:g.56884184_56884185del
NG_009386.2:g.23978_23979del
NM_000339.3:c.1805_1806del
NM_001126107.2:c.1802_1803del
NM_001126108.2:c.1805_1806delMANE SELECT
NP_000330.3:p.Tyr602fs
NP_001119579.2:p.Tyr601fs
NP_001119580.2:p.Tyr602fs
NC_000016.9:g.56918095_56918096del
NC_000016.9:g.56918096_56918097del
NG_009386.1:g.23978_23979del

Protein change:

Y601fs

Links:

dbSNP: rs2144723594

NCBI 1000 Genomes Browser:

rs2144723594

Molecular consequence:

NM_000339.3:c.1805_1806del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126107.2:c.1802_1803del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126108.2:c.1805_1806del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001586749	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 10, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20848653, 22009145, 25841442, 15069170, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001586749

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 10, 2023)

germline

clinical testing

PubMed (5)
[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

Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.

Yang SS, Lo YF, Yu IS, Lin SW, Chang TH, Hsu YJ, Chao TK, Sytwu HK, Uchida S, Sasaki S, Lin SH.

Hum Mutat. 2010 Dec;31(12):1304-15. doi: 10.1002/humu.21364. Epub 2010 Oct 14.

PubMed [citation]

PMID:: 20848653

Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome.

Glaudemans B, Yntema HG, San-Cristobal P, Schoots J, Pfundt R, Kamsteeg EJ, Bindels RJ, Knoers NV, Hoenderop JG, Hoefsloot LH.

Eur J Hum Genet. 2012 Mar;20(3):263-70. doi: 10.1038/ejhg.2011.189. Epub 2011 Oct 19.

PubMed [citation]

PMID:: 22009145
PMCID:: PMC3283182

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001586749.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Tyr602Cysfs*31) in the SLC12A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Gitelman syndrome (PMID: 15069170). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1073479). For these reasons, this variant has been classified as Pathogenic.

#	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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