Submissions for variant NM_001009944.3(PKD1):c.1523G>T (p.Cys508Phe)

dbSNP: rs1057518001

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413480	SCV000491349	likely pathogenic	not provided	2016-06-24	criteria provided, single submitter	clinical testing	The C508F variant in the PKD1 gene has not been reported previously as a pathogenic variant, nor as a benignvariant, to our knowledge. The C508F variant was not observed in approximately 3,500 individuals of European andAfrican American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant inthese populations. The C508F variant is a non-conservative amino acid substitution, which is likely to impactsecondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitutionoccurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging tothe protein structure/function. A missense variant in the same residue (C508R) has been reported in the Human GeneMutation Database in association with polycystic kidney disease (Rosetti et al., 2003; Stenson et al., 2014),supporting the functional importance of this region of the protein. Therefore, the C508F variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.