a nonsense variant, a variant changing an amino acid to a translation termination (stop) codon, is described as a substitution.
NOTE: a nonsense variant is not described as a Deletion of the C-terminal end of the protein (e.g. p.Trp26_Arg1623del)
amino acids that have been tested and found not changed are described as p.Cys123= (see SVD-WG001 (no change)). NOTE: the underlying DNA change must be given in addition and in this case is either c.456C>T or c.456C= NOTE: such changes are silent protein changes
the description p.Arg76_Cys77delinsSerTrp is preferred over p.[Arg76Ser;Cys77Trp]. NOTE: by definition this change can not be described as a substitution (like p.Arg76_Cys77SerTrp)
it is not correct to describe “polymorphisms” as p.76Ser/Arg (see Discussions).
amino acid Trp24 is changed to a Cys
amino acid Trp24is predicted to change to a Cys (no experimental proof, e.g. based on DNA level data)
amino acid Trp24 is changed to a stop codon (Ter, *) NOTE: this change is not described as a deletion of the C-terminal end of the protein (i.e. p.Trp24_Met36853del)
amino acid Cys188 is not changed (DNA level change ..TGC.. to ..TGT..)
translation initiation codon
description depends on the consequences of the change on the translation product (protein);
as a consequence of a variant no protein is produced
the consequence of a variant at the protein level are not known (can not be predicted)
a variant causes the inactivation of the normal and activation of a downstream translation initiation site (Met) resulting in deletion of the first 123 amino acids (Met-1 to Val-123) of the protein. NOTE: the 3’ rule applies.
amino acid Gly56 is changed to an Ala, Ser or Cys (see Uncertain)
Are polymorphisms described like p.2366Gln/Lys?
No, all substitutions are described as NP_003997.1:p.Gln2366Lys. In the past, the format p.2366Gln/Lys (p.2366Q/K) has been used to describe "polymorphic" sequence variants. Note that a description should be neutral, simply describe the change, and not include any other information like predicted or known functional consequences.
Can I describe a TrpVal to CysArg variant as a amino acid substitution (p.TrpVal24CysArg)?
No, this is not allowed. By definition a substitution changes one amino acid into one other amino acid. The change TrpVal to CysArg should be described as NP_003997.1:p.Trp24_Val25delinsCysArg, i.e. a deletion/insertion (indel) (see Deletion-Insertion).