Table 4.

PKD1 variants identified in patients with subsequent clinical or genetic diagnosis of ADPKD in a parent or close relative.

cDNA Position	Codon Change	Mutation Type	Splice score	Amino acid conservation score(Conseq)	Predicted effect of amino acid change(Polyphen)	Family	Present in Parent	Reference
c.10526C>T	p.Thr3509Met	Missense		5b	Possibly damaging	2968	Yes	19,20
c.11534+2_11534+3insGGG		Splice	7.7a			2688	Yes	18
c.12742delC	p.Arg4248AlafsX56	Truncating				818	Yes	This report

The reference sequence used in describing these variants is NM_000296.2; the numbering begins with the first nucleotide of the coding sequence (i.e. A of ATG codon is +1). Accordingly, c.11534+2_11534+3insGGG describes an insertion of nucleotides GGG occurring in intron 41, between 3 and 4 bases beyond coding nucleotide 11,534. All protein alterations were deduced based on changes in DNA sequence. Protein change p.Arg4248AlafsX56 refers to an arginine to alanine frameshift occurring at amino acid 4,248 resulting in a premature stop codon at the following 56^th codon caused by deletion of coding nucleotide 12,742 (c.12742delC).

^aThe splice score compares how closely the splice site DNA sequence fits the consensus splice site sequence. The splice score for a perfect match for a 5′ site is 12.6 and the mean score for consecutive exons is 8.1. Lower values reflect a poorer match between the variant sequence and consensus splice site.¹⁷

^bThe amino acid conservation scale reported for Conseq analysis ranges from 1–9, where a score of 1 is variable, 9 is evolutionarily conserved and 5 average.¹⁶