U.S. flag

An official website of the United States government

NM_001377299.1(NDUFS2):c.422A>G (p.Tyr141Cys) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 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:
RCV003994270.2

Allele description [Variation Report for NM_001377299.1(NDUFS2):c.422A>G (p.Tyr141Cys)]

NM_001377299.1(NDUFS2):c.422A>G (p.Tyr141Cys)

Gene:
NDUFS2:NADH:ubiquinone oxidoreductase core subunit S2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q23.3
Genomic location:
Preferred name:
NM_001377299.1(NDUFS2):c.422A>G (p.Tyr141Cys)
HGVS:
  • NC_000001.11:g.161209221A>G
  • NG_013352.1:g.14907A>G
  • NM_001166159.2:c.422A>G
  • NM_001377298.1:c.422A>G
  • NM_001377299.1:c.422A>GMANE SELECT
  • NM_001377300.1:c.422A>G
  • NM_001377301.1:c.422A>G
  • NM_001377302.1:c.422A>G
  • NM_004550.5:c.422A>G
  • NP_001159631.1:p.Tyr141Cys
  • NP_001364227.1:p.Tyr141Cys
  • NP_001364228.1:p.Tyr141Cys
  • NP_001364229.1:p.Tyr141Cys
  • NP_001364230.1:p.Tyr141Cys
  • NP_001364231.1:p.Tyr141Cys
  • NP_004541.1:p.Tyr141Cys
  • NC_000001.10:g.161179011A>G
  • NM_004550.4:c.422A>G
  • NR_165188.1:n.441A>G
Protein change:
Y141C
Links:
dbSNP: rs1665635198
NCBI 1000 Genomes Browser:
rs1665635198
Molecular consequence:
  • NM_001166159.2:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377298.1:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377299.1:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377300.1:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377301.1:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377302.1:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004550.5:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_165188.1:n.441A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004814032Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Feb 20, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families.

Tuppen HA, Hogan VE, He L, Blakely EL, Worgan L, Al-Dosary M, Saretzki G, Alston CL, Morris AA, Clarke M, Jones S, Devlin AM, Mansour S, Chrzanowska-Lightowlers ZM, Thorburn DR, McFarland R, Taylor RW.

Brain. 2010 Oct;133(10):2952-63. doi: 10.1093/brain/awq232. Epub 2010 Sep 6.

PubMed [citation]
PMID:
20819849
PMCID:
PMC2947428

Muscle Involvement in a Large Cohort of Pediatric Patients with Genetic Diagnosis of Mitochondrial Disease.

Jou C, Ortigoza-Escobar JD, O'Callaghan MM, Nascimento A, Darling A, Pias-Peleteiro L, Perez-DueƱas B, Pineda M, Codina A, Arjona C, Armstrong J, Palau F, Ribes A, Gort L, Tort F, Navas P, Ruiz-Pesini E, Emperador S, Lopez-Gallardo E, Bayona-Bafaluy P, Montero R, Jimenez-Mallebrera C, et al.

J Clin Med. 2019 Jan 10;8(1). doi:pii: E68. 10.3390/jcm8010068.

PubMed [citation]
PMID:
30634555
PMCID:
PMC6352184
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004814032.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: NDUFS2 c.422A>G (p.Tyr141Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251448 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.422A>G has been reported in the literature in heterozygous individuals without a reported second variant affected with Mitochondrial Complex I Deficiency or Leigh syndrome (e.g. Jou_2019, Tuppen_2010). These reports do not provide unequivocal conclusions about association of the variant with Mitochondrial Complex I Deficiency, Nuclear Type 6. One publication reports experimental evidence evaluating an impact on protein function showing severely decreased levels of dNADH oxidase activity in an E.coli system, however, does not allow convincing conclusions about the variant effect (e.g. Alkhaldi_2023). The following publications have been ascertained in the context of this evaluation (PMID: 36462614, 30634555, 20819849). ClinVar contains an entry for this variant (Variation ID: 1030813). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Sep 29, 2024