Table 3.

PKD1 variants of possible pathogenicity identified in patients with no clinical diagnosis of ADPKD in either parent.

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.107C>A	p.Pro36His	Missense		1.902b	No prediction	2712	Yes	This report
c.3502C>T	p.Pro1168Ser	Missense		5b	Benign	2365	Yes	This report
c.4546G>A	p.Ala1516Thr	Missense		5b	Benign	1193	Yes	This report
c.11014–3C>T		Splice	6.0a			2272	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.107C>A describes a C to A nucleotide substitution occurring at position 107 in the coding sequence that results in substitution of the amino acid histidine for proline at protein position 36 (p.Pro36His). All protein alterations were deduced based on changes in DNA sequence.

^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 3′ site is 14.2 and the mean score for consecutive exons is 7.9. 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