NM_003060.4(SLC22A5):c.364G>T (p.Asp122Tyr) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 23, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000186160.6

Allele description [Variation Report for NM_003060.4(SLC22A5):c.364G>T (p.Asp122Tyr)]

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

Gene:
SLC22A5:solute carrier family 22 member 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.1
Genomic location:
Preferred name:
NM_003060.4(SLC22A5):c.364G>T (p.Asp122Tyr)
Other names:
p.D122Y:GAC>TAC
HGVS:
  • NC_000005.10:g.132370336G>T
  • NG_008982.2:g.5633G>T
  • NM_001308122.1:c.364G>T
  • NM_001308122.2:c.364G>T
  • NM_003060.4:c.364G>TMANE SELECT
  • NP_001295051.1:p.Asp122Tyr
  • NP_001295051.1:p.Asp122Tyr
  • NP_003051.1:p.Asp122Tyr
  • NC_000005.9:g.131706028G>T
  • NM_003060.3:c.364G>T
  • O76082:p.Asp122Tyr
Links:
UniProtKB: O76082#VAR_064118; dbSNP: rs201082652
NCBI 1000 Genomes Browser:
rs201082652
Molecular consequence:
  • NM_001308122.1:c.364G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001308122.2:c.364G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003060.4:c.364G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000224396EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Apr 25, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000239186GeneDxcriteria provided, single submitter
Pathogenic
(Nov 4, 2016)
germlineclinical testing

Citation Link,

SCV001446948Institute of Medical Genetics and Applied Genomics, University Hospital Tübingencriteria provided, single submitter
Pathogenic
(Oct 23, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot provided1not providedclinical testing

Citations

PubMed

Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore.

Toh DS, Yee JY, Koo SH, Murray M, Lee EJ.

Drug Metab Pharmacokinet. 2010;25(1):112-9.

PubMed [citation]
PMID:
20208395

Functional analysis of pharmacogenetic variants of human organic cation/carnitine transporter 2 (hOCTN2) identified in Singaporean populations.

Toh DS, Murray M, Pern Tan K, Mulay V, Grewal T, Lee EJ, Zhou F.

Biochem Pharmacol. 2011 Dec 1;82(11):1692-9. doi: 10.1016/j.bcp.2011.08.008. Epub 2011 Aug 16.

PubMed [citation]
PMID:
21864509
See all PubMed Citations (3)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000224396.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From GeneDx, SCV000239186.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 SLC22A5 variant was not identified, and serum carnitine concentrations were not reported (Li et al., 2010). Functional studies of the D122Y variant found that it resulted in significantly decreased carnitine transport and decreased expression of human organic cation/carnitine transporter 2 in the plasma membrane of transfected cells (Toh el al., 2011). The D122Y variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. The D122Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D122Y as a pathogenic variant.

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446948.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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