Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781512 | SCV000919596 | likely pathogenic | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type | 2018-11-16 | criteria provided, single submitter | clinical testing | Variant summary: LRPPRC c.3130C>T (p.Arg1044X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 246102 control chromosomes (gnomAD). c.3130C>T has been reported in the literature as a case report in at-least one compound heterozygous individual, together with two missense variants (c.3430C>T (p.Arg1144Cys) and c.4078G>A (p.Ala1360Thr). This patient was affected with a milder phenotype of Leigh Syndrome, French-Canadian Type (Han 2017). The variant was incorrectly reported by the authors at the protein-level as p.Arg1044Cys instead of p.Arg1044X, possibly due to a typographical error as the remaining variants seemed to match the single and only canonical transcript for this gene. It also corroborates the annotation in the HGMD database as p.Arg1044X. Therefore, these data do not allow any conclusion about variant significance. To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported, though the patient described by Han et al. 2017 had characteristic muscle biopsy findings demonstrating respiratory complex IV defect. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |