NM_000402.4(G6PD):c.1114C>T (p.Leu372Phe) AND Metachromatic leukodystrophy

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Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 15, 2024
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:: RCV004540994.1

Allele description

NM_000402.4(G6PD):c.1114C>T (p.Leu372Phe)

Gene:

G6PD:glucose-6-phosphate dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000402.4(G6PD):c.1114C>T (p.Leu372Phe)

Other names:

G6PD, LEU342PHE; G6PD Chinese-5; G6PD Mahidol-like

HGVS:

NC_000023.11:g.154532969G>A
NG_009015.2:g.19604C>T
NM_000402.4:c.1114C>T
NM_001042351.3:c.1024C>T
NM_001360016.2:c.1024C>TMANE SELECT
NP_000393.4:p.Leu372Phe
NP_001035810.1:p.Leu342Phe
NP_001035810.1:p.Leu342Phe
NP_001346945.1:p.Leu342Phe
NC_000023.10:g.153761184G>A
NM_001042351.1:c.1024C>T
NM_001042351.3:c.1024C>T

Protein change:

L342F; LEU342PHE

Links:

OMIM: 305900.0046; dbSNP: rs137852342

NCBI 1000 Genomes Browser:

rs137852342

Molecular consequence:

NM_000402.4:c.1114C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042351.3:c.1024C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001360016.2:c.1024C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Metachromatic leukodystrophy (MLD)
Synonyms:: Metachromatic leukoencephalopathy; Sulfatide lipidosis; Cerebral sclerosis diffuse metachromatic form; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018868; MedGen: C0023522; Orphanet: 512; OMIM: 250100

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Homo sapiens dedicator of cytokinesis 7 (DOCK7), transcript variant 5, mRNA
Homo sapiens dedicator of cytokinesis 7 (DOCK7), transcript variant 5, mRNA
gi|1675035473|ref|NM_001272002.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005040778	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 15, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29339739, 36681081, 34659341 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005040778

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 15, 2024)

germline

clinical testing

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

Citation Link

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 of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates.

Fu C, Luo S, Li Q, Xie B, Yang Q, Geng G, Lin C, Su J, Zhang Y, Wang J, Qin Z, Luo J, Chen S, Fan X.

Sci Rep. 2018 Jan 16;8(1):833. doi: 10.1038/s41598-017-17667-6.

PubMed [citation]

PMID:: 29339739
PMCID:: PMC5770456

Functional interpretation, cataloging, and analysis of 1,341 glucose-6-phosphate dehydrogenase variants.

Geck RC, Powell NR, Dunham MJ.

Am J Hum Genet. 2023 Feb 2;110(2):228-239. doi: 10.1016/j.ajhg.2023.01.003. Epub 2023 Jan 20.

PubMed [citation]

PMID:: 36681081
PMCID:: PMC9943724

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040778.1

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

Description

Variant summary: ARSA c.1114C>T (p.Arg372Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250080 control chromosomes. c.1114C>T has been reported in the literature in multiple individuals affected with Metachromatic Leukodystrophy (Biffi_2008, Heinisch_1995, Fumagalli_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was 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

Last Updated: Sep 16, 2024

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