NM_001126108.2(SLC12A3):c.2546T>A (p.Leu849His) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 8, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000713330.4

Allele description [Variation Report for NM_001126108.2(SLC12A3):c.2546T>A (p.Leu849His)]

NM_001126108.2(SLC12A3):c.2546T>A (p.Leu849His)

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.2546T>A (p.Leu849His)
HGVS:
  • NC_000016.10:g.56894555T>A
  • NG_009386.1:g.34349T>A
  • NM_000339.3:c.2573T>A
  • NM_001126107.2:c.2570T>A
  • NM_001126108.2:c.2546T>AMANE SELECT
  • NP_000330.3:p.Leu858His
  • NP_001119579.2:p.Leu857His
  • NP_001119580.2:p.Leu849His
  • NC_000016.9:g.56928467T>A
  • NM_000339.2:c.2573T>A
Protein change:
L849H
Links:
dbSNP: rs185927948
NCBI 1000 Genomes Browser:
rs185927948
Molecular consequence:
  • NM_000339.3:c.2573T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126107.2:c.2570T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126108.2:c.2546T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000843927Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Apr 1, 2016)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV000940176Invitaecriteria provided, single submitter
Pathogenic
(Oct 8, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.

Aoi N, Nakayama T, Tahira Y, Haketa A, Yabuki M, Sekiyama T, Nakane C, Mano H, Kawachi H, Sato N, Soma M, Matsumoto K.

Endocrine. 2007 Apr;31(2):149-53.

PubMed [citation]
PMID:
17873326

Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients with Gitelman's syndrome.

Monkawa T, Kurihara I, Kobayashi K, Hayashi M, Saruta T.

J Am Soc Nephrol. 2000 Jan;11(1):65-70. doi: 10.1681/ASN.V11165.

PubMed [citation]
PMID:
10616841
See all PubMed Citations (13)

Details of each submission

From Athena Diagnostics Inc, SCV000843927.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000940176.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces leucine with histidine at codon 858 of the SLC12A3 protein (p.Leu858His). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and histidine. This variant is present in population databases (rs185927948, ExAC 0.1%). This variant has been observed in several individuals and families with SLC12A3-related conditions (PMID: 21628937, 26041598, 21757836, 15069170, 26770037). This variant has been also observed on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with SLC12A3-related conditions (PMID: 15069170, 21628937). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also know as p.Leu849His. ClinVar contains an entry for this variant (Variation ID: 225470). Experimental studies have shown that this missense change has a deleterious effect on protein function (PMID: 16471174). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Aug 27, 2021

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