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NM_005957.5(MTHFR):c.707T>C (p.Phe236Ser) AND Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 6, 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:
RCV003021228.2

Allele description

NM_005957.5(MTHFR):c.707T>C (p.Phe236Ser)

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.707T>C (p.Phe236Ser)
HGVS:
  • NC_000001.11:g.11796279A>G
  • NG_013351.1:g.14825T>C
  • NM_001330358.2:c.830T>C
  • NM_001410750.1:c.827T>C
  • NM_005957.5:c.707T>CMANE SELECT
  • NP_001317287.1:p.Phe277Ser
  • NP_001397679.1:p.Phe276Ser
  • NP_005948.3:p.Phe236Ser
  • NP_005948.3:p.Phe236Ser
  • LRG_726t1:c.707T>C
  • LRG_726:g.14825T>C
  • LRG_726p1:p.Phe236Ser
  • NC_000001.10:g.11856336A>G
  • NM_005957.4:c.707T>C
Protein change:
F236S
Molecular consequence:
  • NM_001330358.2:c.830T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410750.1:c.827T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005957.5:c.707T>C - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003313360Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Feb 6, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Details of each submission

From Invitae, SCV003313360.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with MTHFR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 236 of the MTHFR protein (p.Phe236Ser).

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

Last Updated: Jun 23, 2024