NM_001164277.2(SLC37A4):c.742C>T (p.Gln248Ter) AND Glucose-6-phosphate transport defect

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 16, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000169082.4

Allele description [Variation Report for NM_001164277.2(SLC37A4):c.742C>T (p.Gln248Ter)]

NM_001164277.2(SLC37A4):c.742C>T (p.Gln248Ter)

Gene:
SLC37A4:solute carrier family 37 member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.3
Genomic location:
Preferred name:
NM_001164277.2(SLC37A4):c.742C>T (p.Gln248Ter)
HGVS:
  • NC_000011.10:g.119026979G>A
  • NG_013331.1:g.8927C>T
  • NM_001164277.1:c.742C>T
  • NM_001164277.2:c.742C>T
  • NM_001164278.2:c.742C>T
  • NM_001164279.2:c.523C>T
  • NM_001164280.2:c.742C>T
  • NM_001467.6:c.742C>T
  • NP_001157749.1:p.Gln248Ter
  • NP_001157749.1:p.Gln248Ter
  • NP_001157750.1:p.Gln248Ter
  • NP_001157751.1:p.Gln175Ter
  • NP_001157752.1:p.Gln248Ter
  • NP_001458.1:p.Gln248Ter
  • LRG_187t1:c.742C>T
  • LRG_187:g.8927C>T
  • LRG_187p1:p.Gln248Ter
  • NC_000011.9:g.118897689G>A
Protein change:
Q175*
Links:
dbSNP: rs781784543
NCBI 1000 Genomes Browser:
rs781784543
Molecular consequence:
  • NM_001164277.1:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001164277.2:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001164278.2:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001164279.2:c.523C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001164280.2:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001467.6:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Glucose-6-phosphate transport defect (GSD1B)
Synonyms:
Glycogen storage disease type 1B; GSD Ib
Identifiers:
MedGen: C0268146; Orphanet: 364; Orphanet: 79259; OMIM: 232220

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000220256Counsylcriteria provided, single submitter
Likely pathogenic
(Apr 21, 2014)
unknownliterature only

PubMed (6)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000697757Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Jul 28, 2016)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000949803Invitaecriteria provided, single submitter
Pathogenic
(Oct 16, 2018)
germlineclinical testing

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

SCV001457665Natera, Inc.no assertion criteria providedPathogenic
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

Melis D, Balivo F, Della Casa R, Romano A, Taurisano R, Capaldo B, Riccardi G, Monsurrò MR, Parenti G, Andria G.

J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S227-31. doi: 10.1007/s10545-008-0810-4. Epub 2008 Apr 21.

PubMed [citation]
PMID:
18437526

Glycogen storage disease type I: diagnosis and phenotype/genotype correlation.

Matern D, Seydewitz HH, Bali D, Lang C, Chen YT.

Eur J Pediatr. 2002 Oct;161 Suppl 1:S10-9. Epub 2002 Jul 27.

PubMed [citation]
PMID:
12373566
See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000220256.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697757.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: The SLC37A4 c.742C>T (p.Gln248X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC37A4 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 2/118148 control chromosomes at a frequency of 0.0000169, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC37A4 variant (0.0012247). This variant has been reported in multiple GSD type 1b patients both homozygously and heterozygously. In addition, one clinical diagnostic laboratory classified this variant as likely pathogenic, without evidence to independently evaluate. Taken together, this variant is classified as pathogenic.

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

From Invitae, SCV000949803.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln248*) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs781784543, ExAC 0.009%). This variant has been observed as a homozygous in individuals affected with glycogen storage disease type Ib (PMID: 9758626, 10026167, 18437526). ClinVar contains an entry for this variant (Variation ID: 188762). Loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). For these reasons, this variant has been classified as Pathogenic.

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

From Natera, Inc., SCV001457665.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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