NM_007103.4(NDUFV1):c.383G>A (p.Arg128Gln) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 28, 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:: RCV003323741.2

Allele description [Variation Report for NM_007103.4(NDUFV1):c.383G>A (p.Arg128Gln)]

NM_007103.4(NDUFV1):c.383G>A (p.Arg128Gln)

Gene:

NDUFV1:NADH:ubiquinone oxidoreductase core subunit V1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_007103.4(NDUFV1):c.383G>A (p.Arg128Gln)

HGVS:

NC_000011.10:g.67609508G>A
NG_013353.1:g.7657G>A
NM_001166102.2:c.356G>A
NM_007103.4:c.383G>AMANE SELECT
NP_001159574.1:p.Arg119Gln
NP_009034.2:p.Arg128Gln
NC_000011.9:g.67376979G>A
NM_007103.3:c.383G>A

Protein change:

R119Q

Links:

dbSNP: rs778295360

NCBI 1000 Genomes Browser:

rs778295360

Molecular consequence:

NM_001166102.2:c.356G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007103.4:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004029038	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31019026, 34645491, 36757698 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004029038

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 28, 2023)

germline

clinical testing

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

Citation Link

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

Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation.

Clark MM, Hildreth A, Batalov S, Ding Y, Chowdhury S, Watkins K, Ellsworth K, Camp B, Kint CI, Yacoubian C, Farnaes L, Bainbridge MN, Beebe C, Braun JJA, Bray M, Carroll J, Cakici JA, Caylor SA, Clarke C, Creed MP, Friedman J, Frith A, et al.

Sci Transl Med. 2019 Apr 24;11(489). doi:pii: eaat6177. 10.1126/scitranslmed.aat6177.

PubMed [citation]

PMID:: 31019026
PMCID:: PMC9512059

Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases.

De La Vega FM, Chowdhury S, Moore B, Frise E, McCarthy J, Hernandez EJ, Wong T, James K, Guidugli L, Agrawal PB, Genetti CA, Brownstein CA, Beggs AH, Löscher BS, Franke A, Boone B, Levy SE, Õunap K, Pajusalu S, Huentelman M, Ramsey K, Naymik M, et al.

Genome Med. 2021 Oct 14;13(1):153. doi: 10.1186/s13073-021-00965-0.

PubMed [citation]

PMID:: 34645491
PMCID:: PMC8515723

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029038.1

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

Description

Variant summary: NDUFV1 c.383G>A (p.Arg128Gln) results in a conservative amino acid change located in the FMN-binding domain (IPR011538) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250842 control chromosomes (gnomAD v2.1 Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.383G>A has been reported in the literature in at least one compound heterozygous individual affected with Leigh Syndrome (e.g., Clark_2019; same patient also described in DeLaVega_2021 and Owen_2023). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31019026, 34645491, 36757698). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic, citing overlapping evidence. Based on the evidence outlined above, the variant was classified as 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: Mar 30, 2024

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