Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV002499536 | SCV002809559 | likely pathogenic | Polycystic kidney disease, adult type | 2022-04-13 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001292527 | SCV001480711 | likely pathogenic | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Ala432Thr variant was identified in 3 of 1890 proband chromosomes (frequency: 0.002) from individuals or families with ADPKD (Heyer 2016). The variant was also identified in the ADPKD Mutation Database (1x as Highly Likely Pathogenic by Athena Diagnostics). The variant was not identified in dbSNP, ClinVar, Clinvitae, LOVD 3.0, or PKD1-LOVD databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). In one study the variant was considered to be a strong mutation based on conservation and chemical change. The p.Ala432 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. 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. |