Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000664807 | SCV000788822 | uncertain significance | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type | 2017-01-05 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001354819 | SCV001549526 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The LRPPRC p.Asn196Thr variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs199727887) and ClinVar (classified as a VUS by Counsyl for Leigh syndrome, French Canadian type). The variant was also identified in control databases in 23 of 282530 chromosomes at a frequency of 0.000081 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 20 of 128914 chromosomes (freq: 0.000155), Other in 1 of 7204 chromosomes (freq: 0.000139), African in 1 of 24958 chromosomes (freq: 0.00004) and European (Finnish) in 1 of 25110 chromosomes (freq: 0.00004), but was not observed in the Latino, Ashkenazi Jewish, East Asian or South Asian populations. The p.Asn196 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |