ClinVar Miner

Submissions for variant NM_004551.3(NDUFS3):c.595C>T (p.Arg199Trp)

gnomAD frequency: 0.00003  dbSNP: rs104894270
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000006391 SCV000930056 likely pathogenic Mitochondrial complex 1 deficiency, nuclear type 8 2019-01-23 criteria provided, single submitter curation This variant is interpreted as a Likely pathogenic for Mitochondrial complex I deficiency, nuclear type 8, autosomal recessive. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:14729820). PS3 : Well-established functional studies show a deleterious effect (PMID:22499348).
Invitae RCV003555941 SCV004294826 pathogenic not provided 2023-08-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 199 of the NDUFS3 protein (p.Arg199Trp). This variant is present in population databases (rs104894270, gnomAD 0.006%). This missense change has been observed in individuals with mitochondrial complex I deficiency (PMID: 14729820, 22499348, 30140060). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6020). 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 NDUFS3 protein function. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006391 SCV000026573 pathogenic Mitochondrial complex 1 deficiency, nuclear type 8 2012-04-01 no assertion criteria provided literature only

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