NM_015506.3(MMACHC):c.619del (p.Asp207fs) AND Cobalamin C disease

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 15, 2020
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:: RCV002037976.5

Allele description

NM_015506.3(MMACHC):c.619del (p.Asp207fs)

Genes:

LOC129930446:ATAC-STARR-seq lymphoblastoid active region 972 [Gene]
MMACHC:metabolism of cobalamin associated C [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_015506.3(MMACHC):c.619del (p.Asp207fs)

HGVS:

NC_000001.11:g.45508985del
NG_013378.1:g.13802del
NM_001330540.2:c.448del
NM_015506.3:c.619delMANE SELECT
NP_001317469.1:p.Asp150fs
NP_056321.2:p.Asp207fs
NC_000001.10:g.45974655del
NC_000001.10:g.45974657del

Protein change:

D150fs

Links:

dbSNP: rs765913293

NCBI 1000 Genomes Browser:

rs765913293

Molecular consequence:

NM_001330540.2:c.448del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_015506.3:c.619del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cobalamin C disease
Synonyms:: Cobalamin-C methylmalonic acidemia and homocystinuria; Methylmalonic acidemia and homocystinuria cblC type; Methylmalonic aciduria and homocystinuria, Vitamin B12-responsive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010184; MedGen: C1848561; Orphanet: 26; Orphanet: 79282; OMIM: 277400

Recent activity

Clear Turn Off Turn On

Human DNA sequence from clone RP5-1117P19 on chromosome 1p31.2-32.3, complete se...
Human DNA sequence from clone RP5-1117P19 on chromosome 1p31.2-32.3, complete sequence
gi|13620289|emb|AL139219.12|

Nucleotide

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
SCV002237066	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 15, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16311595, 19767224, 30157807, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002237066

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 15, 2020)

germline

clinical testing

PubMed (4)
[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

Citations

PubMed

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS.

Nat Genet. 2006 Jan;38(1):93-100. Epub 2005 Nov 27. Erratum in: Nat Genet. 2006 Aug;38(8):957.

PubMed [citation]

PMID:: 16311595

High prevalence of structural heart disease in children with cblC-type methylmalonic aciduria and homocystinuria.

Profitlich LE, Kirmse B, Wasserstein MP, Diaz GA, Srivastava S.

Mol Genet Metab. 2009 Dec;98(4):344-8. doi: 10.1016/j.ymgme.2009.07.017. Epub 2009 Aug 12.

PubMed [citation]

PMID:: 19767224

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002237066.3

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

Description

This sequence change creates a premature translational stop signal (p.Asp207Metfs*3) in the MMACHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the MMACHC protein. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MMACHC protein. Other variant(s) that disrupt this region (p.Tyr222*) have been determined to be pathogenic (PMID: 16311595, 19767224, 30157807). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with MMACHC-related conditions.

#	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

ClinVar

Relating variation to medicine