ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.7429C>T (p.Arg2477Cys) (rs376283361)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000248177 SCV000305775 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000766664 SCV000617183 uncertain significance not provided 2015-10-08 criteria provided, single submitter clinical testing The R2477C variant in the PKD1 gene has been reported previously in an individual with polycystic kidney disease. However, this individual reportedly carried a second missense variant in the PKD1 gene that segregated with the disease, while the R2477C variant reportedly did not segregate with the disease (Rossetti et al., 2007). The R2477C variant was not observed at any significant frequency in approximately 4,800 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R2477C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in the same residue (R2477H) has been reported in association with polycystic kidney disease type 1 (Chang et al., 2013), supporting the functional importance of this residue. We interpret R2477C as a variant of uncertain significance.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626652 SCV000747354 uncertain significance Talipes equinovarus; Polycystic kidney dysplasia; Narrow chest; Hyperechogenic kidneys 2017-01-01 criteria provided, single submitter clinical testing

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