Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779076 | SCV000915547 | uncertain significance | NDUFV1-related disorder | 2018-10-19 | criteria provided, single submitter | clinical testing | The NDUFV1 c.753_756delCCCC (p.Pro252GlnfsTer44) variant is a frameshift variant that is predicted to cause premature truncation of the protein. The variant has been reported in a compound heterozygous state with a second missense variant in one individual affected with Leigh syndrome (Marin et al. 2013). Control data are unavailable for this variant which is reported at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the evidence and the potential impact of frameshift variants, the p.Pro252GlnfsTer44 variant is classified as a variant of unknown significance but suspicious for pathogenicity for NDUFV1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV001856166 | SCV002211789 | pathogenic | not provided | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro252Glnfs*44) in the NDUFV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NDUFV1 are known to be pathogenic (PMID: 10080174, 11349233). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Leigh syndrome (PMID: 23266820). ClinVar contains an entry for this variant (Variation ID: 632170). For these reasons, this variant has been classified as Pathogenic. |
| Laboratory for Molecular Medicine, |
RCV004017737 | SCV004847945 | pathogenic | Leigh syndrome | 2015-04-01 | criteria provided, single submitter | clinical testing | The p.Pro252fs variant in NDUFV1 has been reported in 1 compound heterozygous Caucasian child with Leigh syndrome (Marin 2013) and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 252 and leads to a premature termination codon 44 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Complete loss of NDUFV1 function is an established disease mechanism in Leigh syndrome. In summary, the p.Pro252fs variant meets our criteria to be classified as pathogenic for Leigh syndrome in an autosomal recessive manner (http://pcpgmwww.partners.org/personalizedmedicince/LMM) based upon absence from controls and the predicted impact to the protein. |
| Mayo Clinic Laboratories, |
RCV001856166 | SCV005413998 | pathogenic | not provided | 2024-09-13 | criteria provided, single submitter | clinical testing | PM1, PM2, PVS1 |