NM_005957.5(MTHFR):c.1958C>T (p.Thr653Met) AND Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Germline classification:: Benign (3 submissions)
Last evaluated:: Feb 1, 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:: RCV000534228.19

Allele description [Variation Report for NM_005957.5(MTHFR):c.1958C>T (p.Thr653Met)]

NM_005957.5(MTHFR):c.1958C>T (p.Thr653Met)

Gene:

MTHFR:methylenetetrahydrofolate reductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_005957.5(MTHFR):c.1958C>T (p.Thr653Met)

HGVS:

NC_000001.11:g.11790693G>A
NG_013351.1:g.20411C>T
NM_001330358.2:c.2081C>T
NM_005957.5:c.1958C>TMANE SELECT
NP_001317287.1:p.Thr694Met
NP_005948.3:p.Thr653Met
NP_005948.3:p.Thr653Met
LRG_726t1:c.1958C>T
LRG_726:g.20411C>T
LRG_726p1:p.Thr653Met
NC_000001.10:g.11850750G>A
NM_005957.4:c.1958C>T
P42898:p.Thr653Met

Protein change:

T653M

Links:

UniProtKB: P42898#VAR_018860; dbSNP: rs35737219

NCBI 1000 Genomes Browser:

rs35737219

Molecular consequence:

NM_001330358.2:c.2081C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005957.5:c.1958C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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putative RING finger protein C32D5.10 [Caenorhabditis elegans]
putative RING finger protein C32D5.10 [Caenorhabditis elegans]
gi|25149646|ref|NP_495278.2|

Protein
RecName: Full=Conotoxin Cal1.2; Flags: Precursor
RecName: Full=Conotoxin Cal1.2; Flags: Precursor
gi|374110505|sp|D5KR59.1|CO112_CONC

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000641855	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001455747	Natera, Inc.	no assertion criteria provided	Benign (Sep 16, 2020)	germline	clinical testing
SCV001737364	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jun 10, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000641855

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Feb 1, 2024)

germline

clinical testing

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

SCV001455747

Natera, Inc.

no assertion criteria provided

Benign
(Sep 16, 2020)

germline

clinical testing

SCV001737364

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Jun 10, 2021)

germline

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	no	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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000641855.5

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

From Natera, Inc., SCV001455747.1

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

From Genome-Nilou Lab, SCV001737364.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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