NM_003060.4(SLC22A5):c.1531G>C (p.Glu511Gln) AND Renal carnitine transport defect

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 18, 2022
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:: RCV002675557.3

Allele description [Variation Report for NM_003060.4(SLC22A5):c.1531G>C (p.Glu511Gln)]

NM_003060.4(SLC22A5):c.1531G>C (p.Glu511Gln)

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.1531G>C (p.Glu511Gln)

HGVS:

NC_000005.10:g.132393756G>C
NG_008982.2:g.29053G>C
NM_001308122.2:c.1603G>C
NM_003060.4:c.1531G>CMANE SELECT
NP_001295051.1:p.Glu535Gln
NP_003051.1:p.Glu511Gln
NC_000005.9:g.131729448G>C

Protein change:

E511Q

Molecular consequence:

NM_001308122.2:c.1603G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003060.4:c.1531G>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
SCV002984575	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 18, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34178604, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002984575

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 18, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Newborn screening for carnitine transporter defect in Bavaria and the long-term follow-up of the identified newborns and mothers: Assessing the benefit and possible harm based on 19 ½ years of experience.

Schiergens KA, Weiss KJ, Röschinger W, Lotz-Havla AS, Schmitt J, Dalla Pozza R, Ulrich S, Odenwald B, Kreuder J, Maier EM.

Mol Genet Metab Rep. 2021 Sep;28:100776. doi: 10.1016/j.ymgmr.2021.100776.

PubMed [citation]

PMID:: 34178604
PMCID:: PMC8214137

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002984575.2

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

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. This missense change has been observed in individual(s) with clinical features of primary carnitine deficiency (PMID: 34178604). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 511 of the SLC22A5 protein (p.Glu511Gln). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

Last Updated: Sep 29, 2024

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