NM_001987.5(ETV6):c.1106G>A (p.Arg369Gln) AND Methylmalonic acidemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 21, 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:: RCV004526621.1

Allele description [Variation Report for NM_001987.5(ETV6):c.1106G>A (p.Arg369Gln)]

NM_001987.5(ETV6):c.1106G>A (p.Arg369Gln)

Genes:

LOC126861452:CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:12037195-12038394 [Gene]
ETV6:ETS variant transcription factor 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.2

Genomic location:

Preferred name:

NM_001987.5(ETV6):c.1106G>A (p.Arg369Gln)

Other names:

R369Q

HGVS:

NC_000012.12:g.11884541G>A
NG_011443.1:g.239688G>A
NM_001987.5:c.1106G>AMANE SELECT
NP_001978.1:p.Arg369Gln
NP_001978.1:p.Arg369Gln
LRG_609t1:c.1106G>A
LRG_609:g.239688G>A
LRG_609p1:p.Arg369Gln
NC_000012.11:g.12037475G>A
NM_001987.4:c.1106G>A
P41212:p.Arg369Gln

Protein change:

ARG369GLN

Links:

UniProtKB: P41212#VAR_073323; OMIM: 600618.0004; dbSNP: rs724159946

NCBI 1000 Genomes Browser:

rs724159946

Molecular consequence:

NM_001987.5:c.1106G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Methylmalonic acidemia (MMA)
Synonyms:: Isolated Methylmalonic Acidemia
Identifiers:: MONDO: MONDO:0002012; MeSH: C537358; MedGen: C0268583; Human Phenotype Ontology: HP:0002912

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005039284	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 21, 2024)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 21680795, 21714648, 15806161, 24904105, 18305557, 26102509, 9694803, 24997145, 26522332, 25581430, 27895058 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005039284

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 21, 2024)

germline

clinical testing

PubMed (11)
[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

Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Zhang J, Mullighan CG, Harvey RC, Wu G, Chen X, Edmonson M, Buetow KH, Carroll WL, Chen IM, Devidas M, Gerhard DS, Loh ML, Reaman GH, Relling MV, Camitta BM, Bowman WP, Smith MA, Willman CL, Downing JR, Hunger SP.

Blood. 2011 Sep 15;118(11):3080-7. doi: 10.1182/blood-2011-03-341412. Epub 2011 Jun 16.

PubMed [citation]

PMID:: 21680795
PMCID:: PMC3175785

Clinical effect of point mutations in myelodysplastic syndromes.

Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL.

N Engl J Med. 2011 Jun 30;364(26):2496-506. doi: 10.1056/NEJMoa1013343.

PubMed [citation]

PMID:: 21714648
PMCID:: PMC3159042

See all PubMed Citations (11)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005039284.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

Variant summary: MUT c.1106G>A (p.Arg369His) results in a non-conservative amino acid change located in the Methylmalonyl-CoA mutase, alpha/beta chain, catalytic domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 250696 control chromosomes. c.1106G>A has been reported in the literature in multiple individuals affected with Methylmalonic Acidemia. 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. Five 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: Jun 9, 2024

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