Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000724124 | SCV000230054 | pathogenic | not provided | 2017-05-16 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000178065 | SCV001201991 | pathogenic | Phenylketonuria | 2023-06-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 197125). This variant has not been reported in the literature in individuals affected with PAH-related conditions. This variant is present in population databases (rs794727619, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Trp120Glyfs*75) in the PAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). |
| Victorian Clinical Genetics Services, |
RCV000178065 | SCV002557833 | pathogenic | Phenylketonuria | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as pathogenic. The following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with phenylketonuria (MIM#261600). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2 and v3) <0.01 for a recessive condition (2 heterozygotes, 0 homozygotes). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic twice and likely pathogenic once in ClinVar. A variant affecting a different nucleotide resulting in the same protein change, c.358delT; p.(Trp120Glyfs*75), has been reported in a homozygous individual with phenylketonuria (PMID: 24130151, BIOPKU database). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Baylor Genetics | RCV000178065 | SCV004209645 | likely pathogenic | Phenylketonuria | 2023-07-08 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000178065 | SCV000792183 | likely pathogenic | Phenylketonuria | 2017-06-09 | no assertion criteria provided | clinical testing |