NM_000709.4(BCKDHA):c.1037G>A (p.Arg346His) AND Maple syrup urine disease

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Aug 7, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000180182.20

Allele description [Variation Report for NM_000709.4(BCKDHA):c.1037G>A (p.Arg346His)]

NM_000709.4(BCKDHA):c.1037G>A (p.Arg346His)

Gene:

BCKDHA:branched chain keto acid dehydrogenase E1 subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000709.4(BCKDHA):c.1037G>A (p.Arg346His)

HGVS:

NC_000019.10:g.41423039G>A
NG_013004.1:g.30251G>A
NM_000709.4:c.1037G>AMANE SELECT
NM_001164783.2:c.1034G>A
NP_000700.1:p.Arg346His
NP_000700.1:p.Arg346His
NP_000700.1:p.Arg346His
NP_001158255.1:p.Arg345His
NC_000019.9:g.41928944G>A
NM_000709.3:c.1037G>A

Protein change:

R345H

Links:

dbSNP: rs398123486

NCBI 1000 Genomes Browser:

rs398123486

Molecular consequence:

NM_000709.4:c.1037G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001164783.2:c.1034G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maple syrup urine disease (MSUD)
Identifiers:: MONDO: MONDO:0009563; MeSH: D008375; MedGen: C0024776; Orphanet: 511; OMIM: PS248600

Recent activity

Clear Turn Off Turn On

Homo sapiens potassium inwardly rectifying channel subfamily J member 15 (KCNJ15...
Homo sapiens potassium inwardly rectifying channel subfamily J member 15 (KCNJ15), transcript variant 5, mRNA
gi|1890344373|ref|NM_001276436.2|

Nucleotide
Resf1 retroelement silencing factor 1 [Mus musculus]
Resf1 retroelement silencing factor 1 [Mus musculus]
Gene ID:67246

Gene
67246[uid] AND (alive[prop]) (1)
Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000800558	Counsyl	no assertion criteria provided	Uncertain significance (Jul 5, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001441646	Shieh Lab, University of California, San Francisco	no assertion criteria provided	Likely pathogenic (Oct 19, 2020)	germline	research
SCV002217195	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 7, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21844576, 22593002, 16786533, 28492532
SCV002791173	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 29, 2021)	unknown	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	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Three Korean patients with maple syrup urine disease: four novel mutations in the BCKDHA gene.

Park HD, Lee DH, Hong YH, Kang DH, Lee YK, Song J, Lee SY, Kim JW, Ki CS, Lee YW.

Ann Clin Lab Sci. 2011 Spring;41(2):167-73.

PubMed [citation]

PMID:: 21844576

Molecular genetic analysis of MSUD from India reveals mutations causing altered protein truncation affecting the C-termini of E1α and E1β.

Bashyam MD, Chaudhary AK, Sinha M, Nagarajaram HA, Devi AR, Bashyam L, Reddy EC, Dalal A.

J Cell Biochem. 2012 Oct;113(10):3122-32. doi: 10.1002/jcb.24189.

PubMed [citation]

PMID:: 22593002

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000800558.2

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

From Shieh Lab, University of California, San Francisco, SCV001441646.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002217195.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BCKDHA protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg346 amino acid residue in BCKDHA. Other variant(s) that disrupt this residue have been observed in individuals with BCKDHA-related conditions (PMID: 16786533, 21844576, 22593002), which suggests that this may be a clinically significant amino acid residue. ClinVar contains an entry for this variant (Variation ID: 93336). This missense change has been observed in individual(s) with BCKDHA-related conditions (PMID: 16786533). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 346 of the BCKDHA protein (p.Arg346His).

#	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 Fulgent Genetics, Fulgent Genetics, SCV002791173.1

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

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine