Table 3.
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.
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 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
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