Table 4.
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 56th codon caused by deletion of coding nucleotide 12,742 (c.12742delC).
The 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
The 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