a sequence change where, compared to a reference sequence, one nucleotide is replaced by one other nucleotide.
Format: “prefix”“position_substituted”“reference_nucleotide””>”new_nucleotide”, e.g. r.123a>g
“prefix” = reference sequence used = r. “position_substituted” = position nucleotide sustituted = 123 “reference_nulceotide” = nucleotide at reference position = a ”>” = type of change is a substitution = > “new_nucleotide” = substituted nucleotide = g
prefix reference sequences accepted are r. (coding and non-coding RNA).
the description r.76_77delinsuu is preferred over r.[76a>u;77g>u]. NOTE: by definition this change can not be described as a substitution (like r.76_77ag>uu or r.76ag>uu)
it is not correct to describe “polymorphisms” as r.76a/g (see Discussions).
a substitution of the “a” nucleotide at r.76 with a “c”
a screen was performed showing that nucleotide r.123 was a “c” as in the coding DNA reference sequence (the nucleotide was not changed). Alternative NM_004006.1:r.123c=.
a “a” to “c” substitution 14 nucleotides 5’ of the ATG translation initiation codon
a “u” to “a” substitution 41 nucleotides 3’ of the translation termination codon
two different transcripts, 897u>g and r.832_960del, derive from one variant (LRG_199t1:c.897T>G at the DNA level)
the description r.76_77delinsug is preferred over r.[76a>u;77a>g] NOTE: based on the definition of a substitution, i.e. one nucleotide replaced by one other nucleotide, this change can not be described as a substitution like r.76_77aa>ug or r.76aa>ug
no RNA from the variant allele could be detected
RNA has not been analysed but it is very likely that splicing is affected
an effect on the RNA level is expected but it is not possible to give a reliable prediction of the consequences (RNA not analysed)
Are polymorphisms described like r.76a/g?
No, all substitutions are described as r.76a>g. In the past, the format r.76a/g 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 GC to TG variant as a dinucleotide substitution (r.4gc>ug)?
No, this is not allowed. By definition a substitution changes one nucleotide into one other nucleotide. The change "ugugcca" to "uguugca" should be described as a deletion/insertion (indel) as r.4_5delinsug.