NM_001126108.2(SLC12A3):c.2186G>T (p.Gly729Val) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 30, 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:
RCV001288429.2

Allele description [Variation Report for NM_001126108.2(SLC12A3):c.2186G>T (p.Gly729Val)]

NM_001126108.2(SLC12A3):c.2186G>T (p.Gly729Val)

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.2186G>T (p.Gly729Val)
HGVS:
  • NC_000016.10:g.56887932G>T
  • NG_009386.1:g.27726G>T
  • NG_009386.2:g.27726G>T
  • NM_000339.3:c.2186G>T
  • NM_001126107.2:c.2183G>T
  • NM_001126108.2:c.2186G>TMANE SELECT
  • NP_000330.3:p.Gly729Val
  • NP_001119579.2:p.Gly728Val
  • NP_001119580.2:p.Gly729Val
  • NC_000016.9:g.56921844G>T
  • NM_000339.2:c.2186G>T
Protein change:
G728V
Molecular consequence:
  • NM_000339.3:c.2186G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126107.2:c.2183G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126108.2:c.2186G>T - 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
SCV001475520Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Oct 24, 2019)
unknownclinical testing

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

SCV001577607Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 30, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Eplerenone in the treatment of Gitelman's syndrome.

Morton A.

Intern Med J. 2008 May;38(5):377. doi: 10.1111/j.1445-5994.2008.01664.x. No abstract available.

PubMed [citation]
PMID:
18402569

Outcome of pregnancy in a patient with Gitelman syndrome: a case report.

Talaulikar GS, Falk MC.

Nephron Physiol. 2005;101(2):p35-8. Epub 2005 Jun 20.

PubMed [citation]
PMID:
15976513
See all PubMed Citations (10)

Details of each submission

From Athena Diagnostics Inc, SCV001475520.1

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

Description

The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.

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

From Invitae, SCV001577607.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces glycine with valine at codon 729 of the SLC12A3 protein (p.Gly729Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs373901523, ExAC 0.03%). This variant has been observed in individual(s) with Gitelman syndrome (PMID: 17654016, 11168953, 31672324). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Gly729 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been observed in individuals with SLC12A3-related conditions (PMID: 21415153), which suggests that this may be a clinically significant amino acid residue. 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.

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

Last Updated: May 14, 2021

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