NM_000402.4(G6PD):c.1114C>T (p.Leu372Phe) AND Anemia, nonspherocytic hemolytic, due to G6PD deficiency

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Dec 21, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000991013.18

Allele description [Variation Report for NM_000402.4(G6PD):c.1114C>T (p.Leu372Phe)]

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:: Anemia, nonspherocytic hemolytic, due to G6PD deficiency (CNSHA1)
Synonyms:: Hemolytic anemia due to G6PD deficiency; Favism, susceptibility to; Class I glucose-6-phosphate dehydrogenase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010480; MedGen: C2720289; Orphanet: 466026; OMIM: 300908

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001142104	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001513322	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 12, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 8364584, 10502785, 16329560, 20203002, 30045279, 30315739, 28492532
SCV002599355	Dunham Lab, University of Washington	criteria provided, single submitter (Bayesian ACMG Guidelines, 2018)	Pathogenic (Aug 12, 2022)	inherited	curation	PubMed (10) [See all records that cite these PMIDs] 16927025, 16329560, 11793482, 8471773, 10502785, 30045279, 25541721, 16607506, 31489982, 29300386
SCV003833854	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 21, 2023)	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	unknown	unknown	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	inherited	yes	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene.

Vulliamy T, Beutler E, Luzzatto L.

Hum Mutat. 1993;2(3):159-67. Review.

PubMed [citation]

PMID:: 8364584

Rapid and reliable detection of glucose-6-phosphate dehydrogenase (G6PD) gene mutations in Han Chinese using high-resolution melting analysis.

Yan JB, Xu HP, Xiong C, Ren ZR, Tian GL, Zeng F, Huang SZ.

J Mol Diagn. 2010 May;12(3):305-11. doi: 10.2353/jmoldx.2010.090104. Epub 2010 Mar 4.

PubMed [citation]

PMID:: 20203002
PMCID:: PMC2860466

See all PubMed Citations (15)

Details of each submission

From Mendelics, SCV001142104.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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, SCV001513322.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces leucine with phenylalanine at codon 342 of the G6PD protein (p.Leu342Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 8364584, 10502785, 16329560, 20203002, 30045279, 30315739). This variant is also known as C13184T or Chinese-5. ClinVar contains an entry for this variant (Variation ID: 10405). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Dunham Lab, University of Washington, SCV002599355.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (10)

Description

Variant found in unrelated hemizygotes with deficiency, some with anemia (PS4_M, PP4). Also found in two heterozygous sisters with deficiency who inherited this variant (c.1024C>T) from father and c.383T>C from mother (PP1). Decreased activity in red blood cells (2-39%) (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.994 (odds of pathogenicity 1517, Prior_P 0.1).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003833854.2

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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