Table 2.

De novo DNA variants of presumed pathogenicity in the PKD1 gene identified in 6 patients during screening of 24 ADPKD patients without family history of ADPKD.

Sequence variant	Predicted codon change	Mutation type	Splice score	Amino acid conservation score (Conseq)	Predicted effect of amino acid change(Polyphen)	Family	Present in parent	Reference
c.323_325delAAG	p.Glu108del	In-frame deletion				1866	No	This report
c.4069delC	p.Leu1357TrpfsX9	Truncating				1203	No	This report
c.10217+1G>T		Splice	8.4a			2594	No	This report
c.11173T>C	p.Trp3725Arg	Missense		5b	Probably damaging	2820	No	This report
c.12395_12403del9	p.Leu4133_Arg4135del	In-frame deletion				1118	No	14
c.12528_12529insA	p.Pro4177ThrfsX32	Truncating				2358	No	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.323_325delAAG describes deletion of the bases AAG starting at coding position 323 and c.10217+1G>T describes a G to T nucleotide substitution occurring in intron 31, 1 base beyond coding nucleotide 10,217. All protein alterations were deduced based on changes in DNA sequence. Protein change p.Leu1357TrpfsX9 refers to a leucine to tryptophan frameshift occurring at amino acid 1,357 resulting in a premature stop codon at the following 9^th codon caused by deletion of coding nucleotide 4,069 (c.4069delC). In like manner, p.Pro4177ThrfsX32 refers to a proline to threonine frameshift occurring at amino acid 4,177 resulting in a premature stop codon at the following 32^nd codon caused by insertion of A between coding nucleotides 12,528 and 12,529. (c.12528_12529insA).

^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