NM_002495.4(NDUFS4):c.355G>C (p.Asp119His) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 20, 2024
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:: RCV003558540.1

Allele description [Variation Report for NM_002495.4(NDUFS4):c.355G>C (p.Asp119His)]

NM_002495.4(NDUFS4):c.355G>C (p.Asp119His)

Gene:

NDUFS4:NADH:ubiquinone oxidoreductase subunit S4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q11.2

Genomic location:

Preferred name:

NM_002495.4(NDUFS4):c.355G>C (p.Asp119His)

HGVS:

NC_000005.10:g.53658555G>C
NG_008200.1:g.102921G>C
NM_001318051.2:c.350+12150G>C
NM_002495.4:c.355G>CMANE SELECT
NP_002486.1:p.Asp119His
NC_000005.9:g.52954385G>C
NM_002495.3:c.355G>C
NR_134473.2:n.551G>C
NR_134474.2:n.468G>C
NR_134475.2:n.503G>C

Protein change:

D119H

Links:

dbSNP: rs747359752

NCBI 1000 Genomes Browser:

rs747359752

Molecular consequence:

NM_001318051.2:c.350+12150G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_002495.4:c.355G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134473.2:n.551G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134474.2:n.468G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_134475.2:n.503G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293732	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 20, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19364667, 31386302, 22326555, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293732

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 20, 2024)

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

NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement.

Leshinsky-Silver E, Lebre AS, Minai L, Saada A, Steffann J, Cohen S, Rötig A, Munnich A, Lev D, Lerman-Sagie T.

Mol Genet Metab. 2009 Jul;97(3):185-9. doi: 10.1016/j.ymgme.2009.03.002. Epub 2009 Mar 11.

PubMed [citation]

PMID:: 19364667

Exploring mTOR inhibition as treatment for mitochondrial disease.

Sage-Schwaede A, Engelstad K, Salazar R, Curcio A, Khandji A, Garvin JH Jr, De Vivo DC.

Ann Clin Transl Neurol. 2019 Sep;6(9):1877-1881. doi: 10.1002/acn3.50846. Epub 2019 Aug 6.

PubMed [citation]

PMID:: 31386302
PMCID:: PMC6764630

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004293732.1

#	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 aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 119 of the NDUFS4 protein (p.Asp119His). This variant is present in population databases (rs747359752, gnomAD 0.01%). This missense change has been observed in individual(s) with Leigh syndrome (PMID: 19364667, 31386302). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 587577). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects NDUFS4 function (PMID: 22326555). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Mar 30, 2024

ClinVar

Relating variation to medicine