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NM_000254.3(MTR):c.1812_1812+1insATAC AND Methylcobalamin deficiency type cblG

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 24, 2023
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:
RCV003631009.2

Allele description [Variation Report for NM_000254.3(MTR):c.1812_1812+1insATAC]

NM_000254.3(MTR):c.1812_1812+1insATAC

Gene:
MTR:5-methyltetrahydrofolate-homocysteine methyltransferase [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000254.3(MTR):c.1812_1812+1insATAC
HGVS:
  • NC_000001.11:g.236852637_236852638insATAC
  • NG_008959.1:g.62357_62358insATAC
  • NM_000254.3:c.1812_1812+1insATACMANE SELECT
  • NM_001291939.1:c.1812_1812+1insATAC
  • NM_001291940.2:c.591_591+1insATAC
  • NM_001410942.1:c.1812_1812+1insATAC
  • NC_000001.10:g.237015937_237015938insATAC
Molecular consequence:
  • NM_000254.3:c.1812_1812+1insATAC - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001291939.1:c.1812_1812+1insATAC - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001291940.2:c.591_591+1insATAC - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001410942.1:c.1812_1812+1insATAC - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Methylcobalamin deficiency type cblG (HMAG)
Synonyms:
HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA DUE TO DEFECT IN COBALAMIN METABOLISM, cblG COMPLEMENTATION TYPE; HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE; Functional methionine synthase deficiency type cblG; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009609; MedGen: C1855128; Orphanet: 2170; Orphanet: 622; OMIM: 250940

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004458821Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 24, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency.

Wilson A, Leclerc D, Saberi F, Campeau E, Hwang HY, Shane B, Phillips JA 3rd, Rosenblatt DS, Gravel RA.

Am J Hum Genet. 1998 Aug;63(2):409-14.

PubMed [citation]
PMID:
9683607
PMCID:
PMC1377317

Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.

Watkins D, Ru M, Hwang HY, Kim CD, Murray A, Philip NS, Kim W, Legakis H, Wai T, Hilton JF, Ge B, Doré C, Hosack A, Wilson A, Gravel RA, Shane B, Hudson TJ, Rosenblatt DS.

Am J Hum Genet. 2002 Jul;71(1):143-53. Epub 2002 May 30.

PubMed [citation]
PMID:
12068375
PMCID:
PMC384971
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004458821.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with MTR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser605Ilefs*18) in the MTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTR are known to be pathogenic (PMID: 9683607, 12068375).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024