Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757638 | SCV000885938 | likely pathogenic | not provided | 2017-10-27 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV001536125 | SCV001752843 | pathogenic | Polycystic kidney disease, adult type | 2022-01-02 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics Inc | RCV000757638 | SCV001879415 | likely pathogenic | not provided | 2020-10-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. Computational tools predict that this variant is damaging. |
| Gene |
RCV000757638 | SCV003806025 | uncertain significance | not provided | 2022-11-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26823553, 17582161, 22383692, 29270497, 31740684, 30816285) |
| Department of Pathology and Laboratory Medicine, |
RCV001292526 | SCV001480710 | likely pathogenic | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Gly381Ser variant was identified in 3 of 404 proband chromosomes (frequency: 0.007) from individuals or families with ADPKD (Rossetti 2007). The p.Gly381Ser variant was also identified in the ADPKD Mutation Database (as Highly Likely Pathogenic). The variant was not identified in the following databases: dbSNP, NHLBI Exome Sequencing Project, the Exome Aggregation Consortium, Clinvitae, ClinVar, COGR, MutDB, PKD1-LOVD, or PKD1-LOVD 3.0. The p.Gly381 residue is conserved in mammals but not in more distantly related organisms 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 p.Gly381Ser variant occurs outside of the splicing consensus sequence and 2 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. Furthermore, this variant was identified in Comprehensive Molecular Diagnostics study and was classified as highly likely pathogenic by in silico analysis (Rossetti 2007). In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |