NM_183050.4(BCKDHB):c.1A>T (p.Met1Leu) AND Maple syrup urine disease

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 11, 2024
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:: RCV000666521.5

Allele description [Variation Report for NM_183050.4(BCKDHB):c.1A>T (p.Met1Leu)]

NM_183050.4(BCKDHB):c.1A>T (p.Met1Leu)

Gene:

BCKDHB:branched chain keto acid dehydrogenase E1 subunit beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q14.1

Genomic location:

Preferred name:

NM_183050.4(BCKDHB):c.1A>T (p.Met1Leu)

HGVS:

NC_000006.12:g.80106694A>T
NG_009775.2:g.5068A>T
NM_000056.5:c.1A>T
NM_001318975.1:c.-15+11A>T
NM_183050.4:c.1A>TMANE SELECT
NP_000047.1:p.Met1Leu
NP_898871.1:p.Met1Leu
NC_000006.11:g.80816411A>T
NM_183050.2:c.1A>T
NR_134945.2:n.24A>T

Protein change:

M1L

Links:

dbSNP: rs1005542482

NCBI 1000 Genomes Browser:

rs1005542482

Molecular consequence:

NM_000056.5:c.1A>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_183050.4:c.1A>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001318975.1:c.-15+11A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000056.5:c.1A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_183050.4:c.1A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_134945.2:n.24A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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
SCV000790826	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Apr 11, 2017)	unknown	clinical testing	Citation Link,
SCV002196332	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26257134, 31980395, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000790826

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Apr 11, 2017)

unknown

clinical testing

Citation Link,

SCV002196332

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2024)

germline

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of mutations, genotype-phenotype correlation and prenatal diagnosis of maple syrup urine disease in Indian patients.

Gupta D, Bijarnia-Mahay S, Saxena R, Kohli S, Dua-Puri R, Verma J, Thomas E, Shigematsu Y, Yamaguchi S, Deb R, Verma IC.

Eur J Med Genet. 2015 Sep;58(9):471-8. doi: 10.1016/j.ejmg.2015.08.002. Epub 2015 Aug 7.

PubMed [citation]

PMID:: 26257134

Branched-chain α-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes.

Strauss KA, Carson VJ, Soltys K, Young ME, Bowser LE, Puffenberger EG, Brigatti KW, Williams KB, Robinson DL, Hendrickson C, Beiler K, Taylor CM, Haas-Givler B, Chopko S, Hailey J, Muelly ER, Shellmer DA, Radcliff Z, Rodrigues A, Loeven K, Heaps AD, Mazariegos GV, et al.

Mol Genet Metab. 2020 Mar;129(3):193-206. doi: 10.1016/j.ymgme.2020.01.006. Epub 2020 Jan 16.

PubMed [citation]

PMID:: 31980395

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000790826.2

#	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, SCV002196332.4

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

Description

This sequence change affects the initiator methionine of the BCKDHB mRNA. The next in-frame methionine is located at codon 71. This variant is present in population databases (no rsID available, gnomAD 0.004%). Disruption of the initiator codon has been observed in individual(s) with maple syrup urine disease (PMID: 26257134, 31980395; Invitae). ClinVar contains an entry for this variant (Variation ID: 551456). For these reasons, this variant has been 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 29, 2024

ClinVar

Relating variation to medicine