NM_003060.4(SLC22A5):c.1554del (p.Asp519fs) AND Renal carnitine transport defect

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 20, 2024
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:: RCV000666861.10

Allele description [Variation Report for NM_003060.4(SLC22A5):c.1554del (p.Asp519fs)]

NM_003060.4(SLC22A5):c.1554del (p.Asp519fs)

Gene:

SLC22A5:solute carrier family 22 member 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q31.1

Genomic location:

Preferred name:

NM_003060.4(SLC22A5):c.1554del (p.Asp519fs)

HGVS:

NC_000005.10:g.132393779del
NG_008982.2:g.29076del
NM_001308122.2:c.1626del
NM_003060.4:c.1554delMANE SELECT
NP_001295051.1:p.Asp543fs
NP_003051.1:p.Asp519fs
NC_000005.9:g.131729471del
NM_003060.3:c.1554del
NM_003060.3:c.1554delA

Protein change:

D519fs

Links:

dbSNP: rs1554088578

NCBI 1000 Genomes Browser:

rs1554088578

Molecular consequence:

NM_001308122.2:c.1626del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003060.4:c.1554del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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carboxy terminal-processing peptidase [Tahibacter amnicola]
carboxy terminal-processing peptidase [Tahibacter amnicola]
gi|2308861029|gnl|PRJNA880161|N4264 5|gb|UXI67993.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000791224	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 4, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001198043	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 20, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17126586, 28492532
SCV002055835	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 15, 2021)	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

SCV000791224

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 4, 2017)

unknown

clinical testing

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

Citation Link,

SCV001198043

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 20, 2024)

germline

clinical testing

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

SCV002055835

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 15, 2021)

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	no	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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2.

Kato Y, Sai Y, Yoshida K, Watanabe C, Hirata T, Tsuji A.

Mol Pharmacol. 2005 Mar;67(3):734-43. Epub 2004 Nov 2.

PubMed [citation]

PMID:: 15523054

Expanded newborn screening identifies maternal primary carnitine deficiency.

Schimmenti LA, Crombez EA, Schwahn BC, Heese BA, Wood TC, Schroer RJ, Bentler K, Cederbaum S, Sarafoglou K, McCann M, Rinaldo P, Matern D, di San Filippo CA, Pasquali M, Berry SA, Longo N.

Mol Genet Metab. 2007 Apr;90(4):441-5. Epub 2006 Nov 28.

PubMed [citation]

PMID:: 17126586

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000791224.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001198043.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Asp519Thrfs*7) in the SLC22A5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acid(s) of the SLC22A5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC22A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 551727). This variant disrupts a region of the SLC22A5 protein in which other variant(s) (p.Ile521Hisfs*3) have been determined to be pathogenic (PMID: 17126586). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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 Genome-Nilou Lab, SCV002055835.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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