Novel GUCY2D Gene Mutations in Japanese Male Twins with Leber Congenital Amaurosis

Table 3

Characteristics of potential pathogenic mutations identified in this study.

Nucleotide change

Predicted effect

Location in gene

Domain^a

Conservation across species^b

Control allele frequency

SNP ID

Computational prediction^c

SIFT

PolyPhen2

PMut

SNAP

Align-GVGD

Splicing

c.2113+2_2113+3insT

Intron 10

Not applicable

0/400

Not present

Missense

c.2714T>C

p.L905P

Exon 14

CD

L/L/L/L/L/L/L

0/400

Not present

Damaging (score 0.00)

Probably damaging

Pathological

Nonneutral

C65

indicates RetGC-1 (protein encoded by GUCY2D) domain; CD = catalytic domain.
^bdenotes human/cow/dog/rat/mouse/zebrafish/fruit fly GUCY2D orthologs (sequences selected from the DDBJ/EMBL/GenBank database).
Accession numbers were NM_000180 (human), NM_174548 (cow), NM_001003207 (dog), NM_024380 (rat), NM_008192 (mouse), NM_131866 (zebrafish), and NM_001202237 (fruit fly). L indicates leucine.
^cAll models used to evaluate the missense mutation suggested that the mutation is pathogenic.
The Align-GVGD analysis results are graded from C0 to C65, where C0 indicates a benign mutation and C65 indicates that the mutation is most likely pathogenic.