ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.8276T>C (p.Leu2759Pro)

dbSNP: rs2544746151
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470588 SCV002768789 uncertain significance Polycystic kidney disease, adult type 2020-05-01 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline (exon 23). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (3 heterozygotes, 0 homozygotes). (N) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (REJ domain; PDB) (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0803 - Low previous evidence of pathogenicity in unrelated individuals (1x in a family with ADPKD; PMID: 26823553) (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
PreventionGenetics, part of Exact Sciences RCV004741296 SCV005355152 uncertain significance PKD1-related disorder 2024-08-21 no assertion criteria provided clinical testing The PKD1 c.8276T>C variant is predicted to result in the amino acid substitution p.Leu2759Pro. To our knowledge, this variant has not been reported in a large population database, indicating this variant is rare. The p.Leu2759 residue is highly conserved during evolution. This variant was reported in an individual with polycystic kidney disease (Heyer et al. 2016. PubMed ID: 26823553, Supplemental Table 2). In addition, we have observed this variant in the heterozygous state in a patient tested for polycystic kidney disease at PreventionGenetics (internal data). Although we highly suspect that this variant is pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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