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NM_001126108.2(SLC12A3):c.2864G>C (p.Arg955Pro) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 6, 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:
RCV003679658.2

Allele description [Variation Report for NM_001126108.2(SLC12A3):c.2864G>C (p.Arg955Pro)]

NM_001126108.2(SLC12A3):c.2864G>C (p.Arg955Pro)

Gene:
SLC12A3:solute carrier family 12 member 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q13
Genomic location:
Preferred name:
NM_001126108.2(SLC12A3):c.2864G>C (p.Arg955Pro)
HGVS:
  • NC_000016.10:g.56904402G>C
  • NG_009386.2:g.44196G>C
  • NG_139603.1:g.434G>C
  • NM_000339.3:c.2891G>C
  • NM_001126107.2:c.2888G>C
  • NM_001126108.2:c.2864G>CMANE SELECT
  • NM_001410896.1:c.2861G>C
  • NP_000330.3:p.Arg964Pro
  • NP_001119579.2:p.Arg963Pro
  • NP_001119580.2:p.Arg955Pro
  • NP_001397825.1:p.Arg954Pro
  • NC_000016.9:g.56938314G>C
Protein change:
R954P
Molecular consequence:
  • NM_000339.3:c.2891G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126107.2:c.2888G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126108.2:c.2864G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410896.1:c.2861G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004401275Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 6, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ, Gitleman HJ, Lifton RP.

Nat Genet. 1996 Jan;12(1):24-30.

PubMed [citation]
PMID:
8528245

Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.

Fava C, Montagnana M, Rosberg L, Burri P, Jönsson A, Wanby P, Wahrenberg H, Hulthén UL, Aurell M, Guidi GC, Melander O.

DNA Seq. 2007 Oct;18(5):395-9.

PubMed [citation]
PMID:
17654016
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004401275.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 964 of the SLC12A3 protein (p.Arg964Pro). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg964 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8528245, 17654016, 21415153, 22214629, 30596175). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt SLC12A3 protein function. This variant has not been reported in the literature in individuals affected with SLC12A3-related conditions. This variant is not present in population databases (gnomAD no frequency).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024