NM_005957.5(MTHFR):c.-13-28_-13-27del AND Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 13, 2022
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:: RCV000167585.4

Allele description [Variation Report for NM_005957.5(MTHFR):c.-13-28_-13-27del]

NM_005957.5(MTHFR):c.-13-28_-13-27del

Gene:

MTHFR:methylenetetrahydrofolate reductase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_005957.5(MTHFR):c.-13-28_-13-27del

HGVS:

NC_000001.11:g.11803156_11803157del
NG_008766.1:g.2007_2008del
NG_013351.1:g.7947_7948del
NM_001330358.2:c.111-28_111-27del
NM_005957.5:c.-13-28_-13-27delMANE SELECT
LRG_726:g.7947_7948del
NC_000001.10:g.11863213_11863214del
NM_005957.4:c.-13-28_-13-27delCT

Links:

dbSNP: rs1553188112

NCBI 1000 Genomes Browser:

rs1553188112

Molecular consequence:

NM_001330358.2:c.111-28_111-27del - intron variant - [Sequence Ontology: SO:0001627]
NM_005957.5:c.-13-28_-13-27del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Homocystinuria due to methylene tetrahydrofolate reductase deficiency
Synonyms:: HOMOCYSTINURIA DUE TO DEFICIENCY OF N(5,10)-METHYLENETETRAHYDROFOLATE REDUCTASE ACTIVITY; Homocysteinemia due to MTHFR deficiency; Homocysteinemia due to methylenetetrahydro-folate reductase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009353; MedGen: C1856061; Orphanet: 395; OMIM: 236250

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000218466	University Children's Hospital, University of Zurich	no assertion criteria provided (Clinical disease; enzymatic activity/kinetics in patient fibroblasts)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003472771	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25736335, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000218466

University Children's Hospital, University of Zurich

no assertion criteria provided

(Clinical disease; enzymatic activity/kinetics in patient fibroblasts)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003472771

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2022)

germline

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Insights into severe 5,10-methylenetetrahydrofolate reductase deficiency: molecular genetic and enzymatic characterization of 76 patients.

Burda P, Schäfer A, Suormala T, Rummel T, Bürer C, Heuberger D, Frapolli M, Giunta C, Sokolová J, Vlášková H, Kožich V, Koch HG, Fowler B, Froese DS, Baumgartner MR.

Hum Mutat. 2015 Jun;36(6):611-21. doi: 10.1002/humu.22779. Epub 2015 Apr 27.

PubMed [citation]

PMID:: 25736335

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From University Children's Hospital, University of Zurich, SCV000218466.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003472771.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change falls in intron 1 of the MTHFR gene. It does not directly change the encoded amino acid sequence of the MTHFR protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. ClinVar contains an entry for this variant (Variation ID: 187865). This variant is also known as c.-40_-41delTC. This variant has been observed in individual(s) with methylenetetrahydrofolate reductase deficiency (PMID: 25736335). This variant is not present in population databases (gnomAD no frequency).

#	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

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