NM_000341.4(SLC3A1):c.1400T>C (p.Met467Thr) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Oct 11, 2019
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:: RCV000413736.6

Allele description [Variation Report for NM_000341.4(SLC3A1):c.1400T>C (p.Met467Thr)]

NM_000341.4(SLC3A1):c.1400T>C (p.Met467Thr)

Gene:

SLC3A1:solute carrier family 3 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000341.4(SLC3A1):c.1400T>C (p.Met467Thr)

HGVS:

NC_000002.12:g.44312653T>C
NG_008233.1:g.42196T>C
NM_000341.4:c.1400T>CMANE SELECT
NP_000332.2:p.Met467Thr
NC_000002.11:g.44539792T>C
NM_000341.3:c.1400T>C
Q07837:p.Met467Thr

Protein change:

M467T; MET467THR

Links:

UniProtKB: Q07837#VAR_011427; OMIM: 104614.0001; dbSNP: rs121912691

NCBI 1000 Genomes Browser:

rs121912691

Molecular consequence:

NM_000341.4:c.1400T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Chromosome neighbors for GEO Profiles (Select 19443155) (1)
GEO Profiles
Nucleotide Links for Protein (Select 2462608307) (2)
Nucleotide
Structure for Protein (Select 2462612306) (3)
Structure
"Genetics Laboratory, UDIAT-Centre Diagnostic, Hospital Universit... (4)
"Genetics Laboratory, UDIAT-Centre Diagnostic, Hospital Universitari Parc Tauli"[submitter] AND "ARID1B"[gene]
Search

ClinVar
Taxonomy Links for Nucleotide (Select 1909388242) (1)
Taxonomy

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490814	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 11, 2019)	germline	clinical testing	Citation Link,
SCV001550787	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Pathogenic	unknown	clinical testing
SCV001926463	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001970036	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000490814.1

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

Description

Reported as the most common pathogenic variant in SLC3A1, accounting for 29.3% of disease-causing alleles across multiple ethnic groups (Eggermann et al., 2012); Published functional studies demonstrate the absence of transport activity in mammalian cells transfected with the M467T variant (Bartoccioni et al., 2008); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 14991253, 12234283, 10798361, 8054986, 18332091, 25296721, 9083097, 21677404, 8792820, 12820697, 10805464, 17010017, 30609409, 28812535, 15635077, 22480232, 16138908, 11748844, 28646536, 31589614, 10562926, 30069816, 33226606)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001550787.1

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

Description

The SLC3A1 p.Met467Thr variant was identified in 19 of 782 proband chromosomes (frequency: 0.0448) from individuals or families with Cystinuria and kidney stones (Rhodes_2015_PMID:25964309; Halbritter_2015_PMID:25296721; Popovska-Jankovic_2013_PMID:23532419). The variant was identified in dbSNP (ID: rs121912691) and in ClinVar (classified as pathogenic by 7 submitters including GeneDx and Invitae; associated condition is Cystinuria). The variant was identified in control databases in 682 of 282552 chromosomes (4 homozygous) at a frequency of 0.002414 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 58 of 10362 chromosomes (freq: 0.005597), European (non-Finnish) in 517 of 128916 chromosomes (freq: 0.00401), Other in 19 of 7206 chromosomes (freq: 0.002637), Latino in 35 of 35416 chromosomes (freq: 0.000988), European (Finnish) in 24 of 25124 chromosomes (freq: 0.000955), African in 20 of 24972 chromosomes (freq: 0.000801) and South Asian in 9 of 30610 chromosomes (freq: 0.000294); it was not observed in the East Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Met467 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. However, functional studies using Xenopus oocytes showed M467T mutants to have reduced transport activity (Bartoccioni_2008_PMID:18332091, Chillarâˆšâ‰¥n_1997_PMID:9083097, Calonge_1994_PMID:8054986). In summary, based on the above information this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001926463.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001970036.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

ClinVar

Relating variation to medicine