ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.10903G>C (p.Ala3635Pro)

gnomAD frequency: 0.00001  dbSNP: rs1166642512
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001131 SCV001158272 uncertain significance Polycystic kidney disease, adult type 2019-03-01 criteria provided, single submitter clinical testing The PKD1 c.10903G>C; p.Ala3635Pro variant (rs1166642512), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on two chromosomes (2/239132 alleles) in the Genome Aggregation Database. The alanine at codon 3635 is moderately conserved, but computational analyses (SIFT: tolerated, PolyPhen-2: damaging) predict conflicting effects of this variant on protein structure/function. Another amino acid substitution at this codon (p.Ala3635Asp) has been reported in an individual with polycystic kidney disease, but its clinical significance is uncertain (Mori 2017). Due to limited information, the clinical significance of the p.Ala3635Pro variant is uncertain at this time. References: Mori T et al. Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel. Clin Exp Nephrol. 2017 Feb;21(1):63-75.
PreventionGenetics, part of Exact Sciences RCV003392729 SCV004119139 uncertain significance PKD1-related disorder 2022-09-10 criteria provided, single submitter clinical testing The PKD1 c.10903G>C variant is predicted to result in the amino acid substitution p.Ala3635Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0068% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2143658-C-G). Of note, a different substitution at the same codon defined as p.Ala3635Asp has been reported in individuals with autosomal dominant polycystic kidney disease (ADPKD), but the clinical significance is unknown (Mori et al. 2017. PubMed ID: 26920127; Kim et al. 2019. PubMed ID: 31740684, reported as p.Ala3634Asp at Supplementary Table S6C). At this time, the clinical significance of the p.Ala3635Pro variant in this patient is uncertain due to the absence of conclusive functional and genetic evidence.

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