Table 2.
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 9th 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 32nd codon caused by insertion of A between coding nucleotides 12,528 and 12,529. (c.12528_12529insA).
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