NM_001365088.1(SLC12A6):c.2612G>A (p.Arg871His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 23, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002261501.6

Allele description [Variation Report for NM_001365088.1(SLC12A6):c.2612G>A (p.Arg871His)]

NM_001365088.1(SLC12A6):c.2612G>A (p.Arg871His)

Genes:

LOC126862097:P300/CBP strongly-dependent group 1 enhancer GRCh37_chr15:34531007-34532206 [Gene]
SLC12A6:solute carrier family 12 member 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_001365088.1(SLC12A6):c.2612G>A (p.Arg871His)

Other names:

p.Arg871His

HGVS:

NC_000015.10:g.34238985C>T
NG_007951.1:g.104080G>A
NM_001042494.2:c.2435G>A
NM_001042495.2:c.2435G>A
NM_001042496.2:c.2585G>A
NM_001042497.2:c.2567G>A
NM_001365088.1:c.2612G>AMANE SELECT
NM_005135.2:c.2459G>A
NM_133647.2:c.2612G>A
NP_001035959.1:p.Arg812His
NP_001035960.1:p.Arg812His
NP_001035961.1:p.Arg862His
NP_001035962.1:p.Arg856His
NP_001352017.1:p.Arg871His
NP_005126.1:p.Arg820His
NP_598408.1:p.Arg871His
LRG_270t1:c.2459G>A
LRG_270t2:c.2612G>A
LRG_270:g.104080G>A
LRG_270p1:p.Arg820His
NC_000015.9:g.34531186C>T
NM_133647.1:c.2612G>A

Protein change:

R812H

Links:

dbSNP: rs151155752

NCBI 1000 Genomes Browser:

rs151155752

Molecular consequence:

NM_001042494.2:c.2435G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042495.2:c.2435G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042496.2:c.2585G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042497.2:c.2567G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001365088.1:c.2612G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005135.2:c.2459G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133647.2:c.2612G>A - 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
SCV002541242	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 6, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003456330	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002541242

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 6, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003456330

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Mayo Clinic Laboratories, Mayo Clinic, SCV002541242.1

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

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003456330.1

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 871 of the SLC12A6 protein (p.Arg871His). This variant is present in population databases (rs151155752, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SLC12A6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1693632). 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 SLC12A6 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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