c.574T > C (p.Cys192Arg) | c.1268 C > T (p.Pro423Leu) | ||
---|---|---|---|
Exon | 4 | 8 | |
gnomAD and/or 1000G | Not reported | rs148603002 (Total allele frequency 0.00016) | |
Mutation taster | Disease-causing | ||
SIFT* | Effect | Damaging | |
Score | 0.01 | 0 | |
Conservation | Highly conserved | ||
PremPS | ΔΔG** (kcal mol-1) | 1.89 | 0.99 |
Location | Core | Surface | |
PolyPhen2† | Effect | Probably damaging | |
Score | 0.984 | 0.998 | |
Hope | The mutant residue introduces a positive charge in a buried residue which can lead to protein folding problems. The mutation will cause a loss of hydrophobic interactions in the core of the protein. | The mutated leucine has a bulky side chain that may affect the enzyme conformation and function | |
ACMG/AMP classification | Likely pathogenic (PM2, PM3, PP3, PP4, PP5) | Likely pathogenic (PM2, PM3, PP1, PP3, PP4) |