ClinVar Miner

Submissions for variant NM_024120.5(NDUFAF5):c.749G>T (p.Gly250Val)

gnomAD frequency: 0.00001  dbSNP: rs757043077
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000431261 SCV000515883 likely pathogenic not provided 2023-03-11 criteria provided, single submitter clinical testing Observed with another NDUFAF5 variant on the opposite allele (in trans) in a patient features of NDUFAF5-related disorder in published literature (Simon et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22664328, 22099533, 21607760, 21924235, 23536703, 30581749, 30473481, 34964562, 34177781)
Labcorp Genetics (formerly Invitae), Labcorp RCV000431261 SCV001226001 pathogenic not provided 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 250 of the NDUFAF5 protein (p.Gly250Val). This variant is present in population databases (rs757043077, gnomAD 0.1%). This missense change has been observed in individuals with mitochondrial complex I deficiency (PMID: 21607760). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372253). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NDUFAF5 protein function. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000412492 SCV002811088 likely pathogenic Mitochondrial complex 1 deficiency, nuclear type 16 2021-07-01 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000431261 SCV002817323 pathogenic not provided 2021-10-08 criteria provided, single submitter clinical testing This variant segregates with disease in multiple families and is considered a founder variant among individuals of Ashkenazi Jewish ancestry (PMID: 21607760). The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). Computational tools yielded predictions that this amino acid change may be damaging to the protein.This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Baylor Genetics RCV000412492 SCV004192011 pathogenic Mitochondrial complex 1 deficiency, nuclear type 16 2024-03-21 criteria provided, single submitter clinical testing
OMIM RCV000412492 SCV000490328 pathogenic Mitochondrial complex 1 deficiency, nuclear type 16 2021-06-06 no assertion criteria provided literature only
Division of Human Genetics, Children's Hospital of Philadelphia RCV000477759 SCV000536831 likely pathogenic Mitochondrial complex I deficiency 2016-01-15 no assertion criteria provided research

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