ClinVar Miner

Submissions for variant NM_025152.3(NUBPL):c.311T>C (p.Leu104Pro)

gnomAD frequency: 0.00006  dbSNP: rs201430951
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000191115 SCV000245519 likely pathogenic Mitochondrial complex I deficiency 2013-08-27 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it once in our laboratory in trans with a pathogenic variant (c.[166G>A;815-27T>C]) in an 18-year-old male with mitochondrial disease
Ambry Genetics RCV000210568 SCV000262856 pathogenic Inborn genetic diseases 2013-01-30 criteria provided, single submitter clinical testing
Zeviani Lab, University of Cambridge RCV000786780 SCV000924645 pathogenic Mitochondrial complex 1 deficiency, nuclear type 21 2019-06-26 criteria provided, single submitter research Complex I deficiency. Found as compound heterozygous with c.726C>G (p.Phe242Leu).
GeneDx RCV000676602 SCV001821127 pathogenic not provided 2023-06-22 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, as expression of this variant in E. coli found that it is associated with reduced protein expression and reduced complex I activity and oxidoreductase activity (Maclean et al., 2018); 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: 25356970, 29982452, 30897263, 31787496, 32518176, 26633545)
Revvity Omics, Revvity RCV000786780 SCV002020565 pathogenic Mitochondrial complex 1 deficiency, nuclear type 21 2021-06-14 criteria provided, single submitter clinical testing
Invitae RCV000676602 SCV003442283 pathogenic not provided 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 104 of the NUBPL protein (p.Leu104Pro). This variant is present in population databases (rs201430951, gnomAD 0.04%). This missense change has been observed in individuals with clinical features of mitochondrial complex I deficiency (PMID: 25356970, 30897263, 31787496, 32518176). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 209179). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects NUBPL function (PMID: 29982452). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000676602 SCV000802390 uncertain significance not provided 2016-03-11 no assertion criteria provided clinical testing
OMIM RCV000786780 SCV001759968 pathogenic Mitochondrial complex 1 deficiency, nuclear type 21 2021-07-21 no assertion criteria provided literature only

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