Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000516248 | SCV000614560 | pathogenic | not provided | 2021-02-24 | 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. This variant has been confirmed to occur de novo in one individual with clinical features associated with this gene. Computational tools predict that this variant is damaging. |
| Cavalleri Lab, |
RCV001095636 | SCV001251277 | uncertain significance | Polycystic kidney disease, adult type | 2020-02-05 | criteria provided, single submitter | research | PM2, PP3, PP4, PP5 |
| Fulgent Genetics, |
RCV001095636 | SCV001752542 | pathogenic | Polycystic kidney disease, adult type | 2021-06-30 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV001095636 | SCV003842089 | likely pathogenic | Polycystic kidney disease, adult type | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.84; 3Cnet: 0.78). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PKD1 related disorder (ClinVar ID: VCV000448027 / PMID: 24611717). The variant has been observed in at least two similarly affected unrelated individuals (PMID: 31740684). A different missense change at the same codon (p.Thr3135Ala) has been reported to be associated with PKD1 related disorder (PMID: 27499327). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Department of Pathology and Laboratory Medicine, |
RCV001292225 | SCV001481033 | uncertain significance | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Thr3135Met variant was identified in 2 of 396 proband chromosomes (frequency: 0.005) from individuals or families with ADPKD and was not identified in 100 control chromosomes from healthy individuals (Bataille 2011, Kurashige 2015). The variant was also identified in dbSNP (ID: rs1555449635), ClinVar (classified as likely pathogenic by Athena Diagnostics), LOVD 3.0 (1x as likely pathogenic), ADPKD Mutation Database (as likely pathogenic) and PKD1-LOVD. The variant was not identified in the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Thr3135 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume 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. |