Table 2.
CPS1 gene variants and pathogenic analysis of seven cases with CPS1 deficiency
| Patient | Allele | Extron (E)/ Intron (I) | Nucleotide changea, b | Amino acid substitutionsb | ACMG/AMP grading | In silico prediction | References | ClinVar accession number | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Mutation Taster | Poly-Phen2e | SIFTf | ||||||||
| 1 | paternal | E20 | c.2493delA | p.Glu832Asnfs*6 | P | / | / | / | This study | SCV003762247 |
| maternal | E32 | c.3793 C > T | p.Pro1265Ser | LP | Disease causing | 1.000 | 0.001 | This study | SCV003762254 | |
| 2 | paternal | I23 | c.2895 + 2T > C | / | LP | / | / | / | This study | SCV003762248 |
| maternal | E2 | c.149T > C | p.Leu50Pro | LP | Disease causing | 1.000 | 0.000 | This study | SCV003762244 | |
| 3 | paternal | E29 | c.3506_3508del | p.Val1170- | P | / | / | / | This study | SCV003762253 |
| maternal | E29 | c.3503 A > T | p.Lys1168Ile | VUS | Disease causing | 1.000 | 0.000 | This study | SCV003762252 | |
| 4 | paternal | E25 | c.3029 C > Tc | p.Thr1010Metc | VUS | / | / | / | [12] | / |
| maternal | E6 | c.616 A > T | p.Thr206Ser | VUS | Disease causing | 0.740 | 0.033 | This study | SCV003762245 | |
| 5 and 7 | paternal | E25 | c.3067dup | p.Asp1023Glyfs*3 | P | / | / | / | This study | SCV003762250 |
| maternal | E13 | c.1294G > A | p.Gly432Ser | VUS | Disease causing | 1.000 | 0.001 | This study | SCV003762246 | |
| 6 | paternal | E11 | c.1145 C > Td | p.Pro382Leud | P | / | / | / | [11] | / |
| maternal | E26 | c.3241del | p.Leu1081Cysfs*19 | P | / | / | / | This study | SCV003762251 | |
P pathogenic, LP likely pathogenic, VUS a variant of unknown significance
aThe reference transcript is NM_001875.4
bUnless indicated with another footnote, this change has been reported first in the present study
cChange reported in Rodriguez-Flores et al. Hum Mutat. 2014;35:105
dChange reported in (1) Häberle et al. Hum Mutat. 2011;32:579; (2) Funghini et al. Gene. 2012;493:228; (3) Liu et al. Hum Mutat. 2021;42:1443; (4) Fan et al. J Clin Lab Anal. 2020;34:e23124
ePolyphen-2 grades the probability of a damaging effect of an amino acid substitution as 0.85-1.00 = probable damaging, 0.15–0.84 = possibly damaging, and 0-0.14 = benign
fSIFT scores the substitution as ≤ 0.05 = damaging, which means the change is predicted to affect protein function
ACMG/AMP, American College of Medical Genetics and Genomics and the Association for Molecular Pathology