NM_205861.3(DHDDS):c.632G>A (p.Arg211Gln) AND Retinitis pigmentosa 59

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 14, 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:: RCV001853833.6

Allele description [Variation Report for NM_205861.3(DHDDS):c.632G>A (p.Arg211Gln)]

NM_205861.3(DHDDS):c.632G>A (p.Arg211Gln)

Gene:

DHDDS:dehydrodolichyl diphosphate synthase subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_205861.3(DHDDS):c.632G>A (p.Arg211Gln)

HGVS:

NC_000001.11:g.26457880G>A
NG_029786.1:g.30599G>A
NM_001243564.2:c.530G>A
NM_001243565.2:c.515G>A
NM_001319959.2:c.353G>A
NM_024887.4:c.632G>A
NM_205861.3:c.632G>AMANE SELECT
NP_001230493.1:p.Arg177Gln
NP_001230493.1:p.Arg177Gln
NP_001230494.1:p.Arg172Gln
NP_001306888.1:p.Arg118Gln
NP_079163.2:p.Arg211Gln
NP_079163.2:p.Arg211Gln
NP_995583.1:p.Arg211Gln
NC_000001.10:g.26784371G>A
NM_001243564.1:c.530G>A
NM_024887.3:c.632G>A

Protein change:

R118Q; ARG211GLN

Links:

OMIM: 608172.0003; dbSNP: rs1553122926

NCBI 1000 Genomes Browser:

rs1553122926

Molecular consequence:

NM_001243564.2:c.530G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243565.2:c.515G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001319959.2:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024887.4:c.632G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_205861.3:c.632G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Retinitis pigmentosa 59 (RP59)
Identifiers:: MONDO: MONDO:0013468; MedGen: C3151227; Orphanet: 791; OMIM: 613861

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002247161	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29100083, 31440733, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247161

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 14, 2023)

germline

clinical testing

PubMed (3)
[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

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.

Hamdan FF, Myers CT, Cossette P, Lemay P, Spiegelman D, Laporte AD, Nassif C, Diallo O, Monlong J, Cadieux-Dion M, Dobrzeniecka S, Meloche C, Retterer K, Cho MT, Rosenfeld JA, Bi W, Massicotte C, Miguet M, Brunga L, Regan BM, Mo K, Tam C, et al.

Am J Hum Genet. 2017 Nov 2;101(5):664-685. doi: 10.1016/j.ajhg.2017.09.008.

PubMed [citation]

PMID:: 29100083
PMCID:: PMC5673604

Epidemiology and etiology of infantile developmental and epileptic encephalopathies in Tasmania.

Ware TL, Huskins SR, Grinton BE, Liu YC, Bennett MF, Harvey M, McMahon J, Andreopoulos-Malikotsinas D, Bahlo M, Howell KB, Hildebrand MS, Damiano JA, Rosenfeld A, Mackay MT, Mandelstam S, Leventer RJ, Harvey AS, Freeman JL, Scheffer IE, Jones DL, Berkovic SF.

Epilepsia Open. 2019 Sep;4(3):504-510. doi: 10.1002/epi4.12350.

PubMed [citation]

PMID:: 31440733
PMCID:: PMC6698683

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002247161.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 211 of the DHDDS protein (p.Arg211Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant developmental and epileptic encephalopathy (PMID: 29100083, 31440733). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 488193). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DHDDS protein function. For these reasons, this variant has been classified as Pathogenic.

#	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: May 12, 2024

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