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NM_003060.4(SLC22A5):c.364G>T (p.Asp122Tyr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Pathogenic(5);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Nov 19, 2021)
Last evaluated:
Nov 2, 2020
Accession:
VCV000025371.23
Variation ID:
25371
Description:
single nucleotide variant
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NM_003060.4(SLC22A5):c.364G>T (p.Asp122Tyr)

Allele ID
36705
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
5q31.1
Genomic location
5: 132370336 (GRCh38) GRCh38 UCSC
5: 131706028 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_001308122.1:c.364G>T NP_001295051.1:p.Asp122Tyr missense
NC_000005.10:g.132370336G>T
NG_008982.2:g.5633G>T
... more HGVS
Protein change
-
Other names
p.D122Y:GAC>TAC
Canonical SPDI
NC_000005.10:132370335:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00043
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD), exomes 0.00038
Exome Aggregation Consortium (ExAC) 0.00042
Trans-Omics for Precision Medicine (TOPMed) 0.00050
Trans-Omics for Precision Medicine (TOPMed) 0.00040
The Genome Aggregation Database (gnomAD) 0.00048
Links
ClinGen: CA312977
UniProtKB: O76082#VAR_064118
dbSNP: rs201082652
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 6 criteria provided, multiple submitters, no conflicts Nov 2, 2020 RCV000022318.18
Pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 23, 2020 RCV000186160.6
Uncertain significance 1 criteria provided, single submitter Nov 5, 2016 RCV000613614.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SLC22A5 - - GRCh38
GRCh37
586 627

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 04, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000239186.12
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The D122Y pathogenic variant in the SLC22A5 gene has been previously reported in an individual who presented with cardiomyopathy and myopathy, in whom a second … (more)
Pathogenic
(Apr 25, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000224396.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/emvc…
http://www.arup.utah.edu/databas…
Pathogenic
(Nov 02, 2020)
criteria provided, single submitter
Method: clinical testing
Renal carnitine transport defect
Allele origin: germline
Invitae
Accession: SCV000632547.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces aspartic acid with tyrosine at codon 122 of the SLC22A5 protein (p.Asp122Tyr). The aspartic acid residue is moderately conserved and there … (more)
Uncertain significance
(Nov 05, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000712504.2
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (3)
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Asp122Tyr variant in SLC22A5 has been reported in the heterozygous state in 2 individuals with suspected … (more)
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Renal carnitine transport defect
Allele origin: germline
Baylor Genetics
Accession: SCV001162975.1
Submitted: (Sep 27, 2019)
Evidence details
Likely pathogenic
(Oct 09, 2018)
criteria provided, single submitter
Method: clinical testing
Renal carnitine transport defect
Allele origin: germline
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital
Accession: SCV001423613.1
Submitted: (May 21, 2020)
Evidence details
Comment:
[ACMG/AMP: PS3, PM2, PM3, PP3] This alteration is supported by well-established in vitro or in vivo functional studies to have a damaging effect on protein … (more)
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal recessive inheritance)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446948.1
Submitted: (Oct 23, 2020)
Evidence details
Likely pathogenic
(Apr 10, 2020)
criteria provided, single submitter
Method: clinical testing
Renal carnitine transport defect
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000886116.2
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The SLC22A5 c.364G>T; p.Asp122Tyr variant (rs201082652) has been reported in an individual with myopathy, but its clinical significance was not determined (Li 2010). It has … (more)
Uncertain significance
(Dec 15, 2018)
no assertion criteria provided
Method: clinical testing
Renal carnitine transport defect
Allele origin: unknown
Counsyl
Accession: SCV001132488.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (4)
Likely pathogenic
(Aug 26, 2021)
no assertion criteria provided
Method: clinical testing
Renal carnitine transport defect
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002022598.1
Submitted: (Nov 19, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases. Neubauer J European journal of human genetics : EJHG 2017 PMID: 28074886
Functional analysis of pharmacogenetic variants of human organic cation/carnitine transporter 2 (hOCTN2) identified in Singaporean populations. Toh DS Biochemical pharmacology 2011 PMID: 21864509
Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. Li FY Human mutation 2010 PMID: 20574985
Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore. Toh DS Drug metabolism and pharmacokinetics 2010 PMID: 20208395
http://www.arup.utah.edu/database/OCTN2/OCTN2_welcome.php - - - -
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC22A5 - - - -

Text-mined citations for rs201082652...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 28, 2021