NM_001126108.2(SLC12A3):c.2615T>C (p.Met872Thr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 15, 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:: RCV002558156.2

Allele description [Variation Report for NM_001126108.2(SLC12A3):c.2615T>C (p.Met872Thr)]

NM_001126108.2(SLC12A3):c.2615T>C (p.Met872Thr)

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.2615T>C (p.Met872Thr)

HGVS:

NC_000016.10:g.56894624T>C
NG_009386.2:g.34418T>C
NM_000339.3:c.2642T>C
NM_001126107.2:c.2639T>C
NM_001126108.2:c.2615T>CMANE SELECT
NP_000330.3:p.Met881Thr
NP_001119579.2:p.Met880Thr
NP_001119580.2:p.Met872Thr
NC_000016.9:g.56928536T>C
NC_000016.9:g.56928536T>C
NG_009386.1:g.34418T>C
NM_000339.2:c.2642T>C

Protein change:

M872T

Links:

dbSNP: rs752124879

NCBI 1000 Genomes Browser:

rs752124879

Molecular consequence:

NM_000339.3:c.2642T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126107.2:c.2639T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126108.2:c.2615T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003443605	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22009145, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443605

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 15, 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 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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003443605.1

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 881 of the SLC12A3 protein (p.Met881Thr). This variant is present in population databases (rs752124879, gnomAD 0.003%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 22009145). ClinVar contains an entry for this variant (Variation ID: 885394). 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 not expected to disrupt SLC12A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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