NM_003060.4(SLC22A5):c.688T>C (p.Phe230Leu) AND Renal carnitine transport defect

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 22, 2023
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:: RCV000556789.12

Allele description [Variation Report for NM_003060.4(SLC22A5):c.688T>C (p.Phe230Leu)]

NM_003060.4(SLC22A5):c.688T>C (p.Phe230Leu)

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.688T>C (p.Phe230Leu)

HGVS:

NC_000005.10:g.132385363T>C
NG_008982.2:g.20660T>C
NM_001308122.2:c.760T>C
NM_003060.4:c.688T>CMANE SELECT
NP_001295051.1:p.Phe254Leu
NP_003051.1:p.Phe230Leu
NC_000005.9:g.131721055T>C
NM_003060.3:c.688T>C

Protein change:

F230L

Links:

dbSNP: rs756650860

NCBI 1000 Genomes Browser:

rs756650860

Molecular consequence:

NM_001308122.2:c.760T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003060.4:c.688T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Renal carnitine transport defect (CDSP)
Synonyms:: CARNITINE TRANSPORTER, PLASMA-MEMBRANE, DEFICIENCY OF; Primary carnitine deficiency; Carnitine uptake defect; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008919; MedGen: C0342788; Orphanet: 158; OMIM: 212140

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000632565	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28841266, 20574985, 28492532
SCV002811585	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 18, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004203593	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 22, 2023)	unknown	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

SCV000632565

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002811585

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 18, 2021)

unknown

clinical testing

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

SCV004203593

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 22, 2023)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional and molecular studies in primary carnitine deficiency.

Frigeni M, Balakrishnan B, Yin X, Calderon FRO, Mao R, Pasquali M, Longo N.

Hum Mutat. 2017 Dec;38(12):1684-1699. doi: 10.1002/humu.23315. Epub 2017 Sep 14.

PubMed [citation]

PMID:: 28841266
PMCID:: PMC5665702

Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency.

Li FY, El-Hattab AW, Bawle EV, Boles RG, Schmitt ES, Scaglia F, Wong LJ.

Hum Mutat. 2010 Aug;31(8):E1632-51. doi: 10.1002/humu.21311.

PubMed [citation]

PMID:: 20574985

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000632565.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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 expected to disrupt SLC22A5 protein function. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SLC22A5 function (PMID: 28841266). ClinVar contains an entry for this variant (Variation ID: 460412). This missense change has been observed in individual(s) with carnitine deficiency (PMID: 20574985; Invitae). This variant is present in population databases (rs756650860, gnomAD 0.004%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 230 of the SLC22A5 protein (p.Phe230Leu).

#	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 Fulgent Genetics, Fulgent Genetics, SCV002811585.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004203593.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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