Table 3.
Combination of Alleles Producing Attenuated Phenotypes*
| Base changea (first allele) | Amino acid changeb | Factors defined as attenuated | Base change (second allele) | Amino acid change |
|---|---|---|---|---|
| c.112T>G | p.C38G | 3 | c.1876T>C | p.Y626H |
| c.455A>C | p.D152G | 4 | c.1618G>A | p.E540K |
| c.526C>T | p.L176F | 1,2,3 | c.526C>T | p.L176F |
| c.1050G>C | p.K350N | 3 | c.1730G>T | p.R577L |
| c.1061C>T | p.A354V | 3 | c.1831C>T | p.R611W |
| c.1144C>T | p.R382C | 1,3 | c.1144C>T | p.R382C |
| c.1145G>A | p.R382H | 2,3 | c.1523A>G | p.Y508C |
| c.1222C>T | p.P408S | 1,3 | c.1244C>T, c.1222C>T | p.P415L, p.P408S |
| c.1244C>T | p.P415L | 1,3 | c.1244C>T, c.1222C>T | p.P415L, p.P408S |
| IVS8+0.6kbdelTC | ? | 3 | p.13376G>A | p.P446X |
| c.1523A>G | p.Y508C | 3 | c.1145G>A | p.R382H |
| c.1730G>T | p.R577L | 3 | c.1050G>C | p.K350N |
| c.1856C>T | p.A619V | 1,3 | c.1856C>T | p.A619V |
| c.1876T>C | p.Y626H | 3 | c.112T>G | p.C38G |
| c.1881G>T | p.W627C | 3,4 | c.1069C>T | p.R357X |
The numbers for the nucleotide changes are reported in accordance with GenBank entry NM_010368.1, NP_034498.1.
The DNA mutation numbering is based on cDNA sequence. Nucleotides numbered from the ATG initiator codons as suggested by den Dunnen and Antonarakis et al. [2001] and per HGVS guidelines (www.hgvs.org).
The correlation of a mutation with an attenuated phenotype is based on four factors: 1) homozygosity of the mutation in the patients with attenuated phenotypes; 2) prediction from the likely structural change in the protein; 3) prediction from in vitro expression studies; and, 4) mutant allele permitting residual enzyme activity in primary fibroblasts or leukocytes, which would be dominant over an allele permitting no activity.