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NM_005629.4(SLC6A8):c.1235_1248del (p.Leu412fs) AND Creatine transporter deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 21, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV003334345.1

Allele description [Variation Report for NM_005629.4(SLC6A8):c.1235_1248del (p.Leu412fs)]

NM_005629.4(SLC6A8):c.1235_1248del (p.Leu412fs)

Gene:
SLC6A8:solute carrier family 6 member 8 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_005629.4(SLC6A8):c.1235_1248del (p.Leu412fs)
Other names:
NM_001142805.2:c.1205_1218del
HGVS:
  • NC_000023.11:g.153693998_153694011del
  • NG_012016.2:g.10702_10715del
  • NM_001142805.2:c.1205_1218del
  • NM_001142806.1:c.890_903del
  • NM_005629.4:c.1235_1248delMANE SELECT
  • NP_001136277.1:p.Leu402fs
  • NP_001136278.1:p.Leu297fs
  • NP_005620.1:p.Leu412fs
  • NC_000023.10:g.152959453_152959466del
Protein change:
L297fs
Molecular consequence:
  • NM_001142805.2:c.1205_1218del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001142806.1:c.890_903del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_005629.4:c.1235_1248del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Creatine transporter deficiency (CCDS1)
Synonyms:
Creatine deficiency, X-linked; Mental retardation , X-linked with seizures, short stature and midface hypoplasia; Mental retardation , X-linked, with creatine transport deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010305; MedGen: C1845862; Orphanet: 52503; OMIM: 300352

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004042606ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen_CCDS_ACMG_Specifications_SLC6A8_v1.1)		Pathogenic
(Jun 21, 2023) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen, SCV004042606.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_005629.4:c.1235_1248del (p.Leu412GlnfsTer48) variant in SLC6A8 is a frameshift variant predicted to cause a premature stop codon, leading to nonsense mediated decay, in a gene in which loss-of-function is an established disease mechanism (PVS1). One male patient, with clinical features consistent with creatine transporter deficiency, elevated urine creatine/creatinine on one occassion, and reduced creatine peak on brain 1H-magnetic resonance spectroscopy, has been reported (PMID: 29435807) (PP4_Strong). The variant is absent in gnomad v2.1.1. (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for creatine transporter deficiency. SLC6A8-specific ACMG/AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PVS1, PP4_Strong, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP, June 21, 2023)

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

Last Updated: Oct 21, 2023