Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Foundation for Research in Genetics and Endocrinology, |
RCV000785878 | SCV000924297 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2019-04-17 | criteria provided, single submitter | clinical testing | The proband had a homozygous p.Pro148Leu variant in the SUCLG1 gene. The variant has previously been reported in an Indian family with an autosomal recessive inheritance. The proband, born of a non-consanguineous marriage, presented with clinical indication of neurological regression with choreoathetoid movements, abnormal movements of limbs, dystonia, hearing deficit, speech delay and elevated levels of blood C5-OH and C4-DC. MRI of his brain revealed white matter changes in the frontoparietal region and posterior putamen signal changes. The variant is not reported in the 1000 Genomes and ExAC databases. In silico prediction of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. In summary, the p.Pro148Leu variant meets our criteria to be classified as an uncertain significant. |
| 3billion | RCV000785878 | SCV002521027 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.79; 3Cnet: 0.66). This variant has been previously reported as uncertain signficance in a similarly affected individual (ClinVar ID: VCV000635004.1) Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. |