NM_052859.4(RFT1):c.200G>A (p.Arg67His) AND RFT1-congenital disorder of glycosylation

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 12, 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:: RCV002524642.2

Allele description [Variation Report for NM_052859.4(RFT1):c.200G>A (p.Arg67His)]

NM_052859.4(RFT1):c.200G>A (p.Arg67His)

Gene:

RFT1:RFT1 homolog [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_052859.4(RFT1):c.200G>A (p.Arg67His)

HGVS:

NC_000003.12:g.53123790C>T
NG_009203.1:g.11665G>A
NM_052859.4:c.200G>AMANE SELECT
NP_443091.1:p.Arg67His
NC_000003.11:g.53157806C>T
NM_052859.3:c.200G>A

Protein change:

R67H

Links:

dbSNP: rs753527390

NCBI 1000 Genomes Browser:

rs753527390

Molecular consequence:

NM_052859.4:c.200G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RFT1-congenital disorder of glycosylation
Synonyms:: CDG In; Congenital disorder of glycosylation type 1N; RFT1-CDG
Identifiers:: MONDO: MONDO:0012783; MedGen: C2677590; Orphanet: 244310; OMIM: 612015

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003524591	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 12, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18313027, 19267216, 30653653, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003524591

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 12, 2022)

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

Human RFT1 deficiency leads to a disorder of N-linked glycosylation.

Haeuptle MA, Pujol FM, Neupert C, Winchester B, Kastaniotis AJ, Aebi M, Hennet T.

Am J Hum Genet. 2008 Mar;82(3):600-6. doi: 10.1016/j.ajhg.2007.12.021. Epub 2008 Feb 28.

PubMed [citation]

PMID:: 18313027
PMCID:: PMC2427296

Comprehensive description of the phenotype of the first case of congenital disorder of glycosylation due to RFT1 deficiency (CDG In).

Clayton PT, Grunewald S.

J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S137-9. doi: 10.1007/s10545-009-1108-x. Epub 2009 Mar 11.

PubMed [citation]

PMID:: 19267216

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003524591.1

#	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 replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 67 of the RFT1 protein (p.Arg67His). This variant is present in population databases (rs753527390, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with RFT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 372948). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg67 amino acid residue in RFT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18313027, 19267216, 30653653). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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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