TABLE 2.
Pathogenic and likely pathogenic 3′ UTR variants by proposed or validated mechanism (n = 26).
| Variant a | Gene | Classification(s) (ClinVar) | Classification (present study) |
|---|---|---|---|
| Altered miRNA binding (n = 7) | |||
| NM_000518.4:c.*32A>C | HBB | P | LP |
| NM_001845.5:c.*35C>A | COL4A1 | P | LP |
| NM_001845.5:c.*32G>T | COL4A1 | P | P |
| NM_001845.5:c.*32G>A | COL4A1 | P | P |
| NM_001845.5:c.*31G>T | COL4A1 | P | LP |
| NM_001281503.1:c.*689G>A | SLITRK1 | P | P |
| NM_006044.3:c.*282A>T | HDAC6 | P | LP |
| Impact on polyadenylation signal (n = 10) | |||
| NM_014017.3:c.*23C>A | LAMTOR2 | P | LP |
| NM_000518.4:c.*110_*114del | HBB | P | LP |
| NM_000518.4:c.*113A>G | HBB | P/LP | LP |
| NM_000518.4:c.*110T>C | HBB | P | P |
| NM_000518.4:c.*110T>A | HBB | P | LP |
| NM_000518.4:c.*93_*105del | HBB | P | LP |
| NM_000517.4:c.*92A>G | HBA2 | P | LP |
| NM_000517.4:c.*94A>G | HBA2 | P | P |
| NM_003491.3:c.*43A>G | NAA10 | LP | LP |
| NM_003491.3:c.*39A>G | NAA10 | P/LP | LP |
| Impact on mRNA stability (n = 3) | |||
| NM_000207.2:c.*59A>G | INS | P | LP |
| NM_003073.4:c.*82C>T | SMARCB1 | P/LP | LP |
| NM_001017980.3:c.*13_*104del | VMA21 | P | LP |
| Altered splicing (n = 1) | |||
| NM_000132.3:c.*56G>T | F8 | LP | LP |
| Impact on secondary structure (n = 1) | |||
| NM_206926.1:c.*1107T>C | SELENON | LP | LP |
| Undetermined mechanism (n = 4) | |||
| NM_000210.3:c.*94_*96del | ITGA6 | LP | LP |
| NM_000518.4:c.*6C>G | HBB | P | P |
| NM_001017980.3:c.*6A>G | VMA21 | P | LP |
| NM_000444.5:c.*231A>G | PHEX | P/LP | LP |
a
Variant HGVS, nomenclature is provided for the APPRIS-defined principal transcript.
LP, likely pathogenic; P, pathogenic; P/LP, P and LP, classifications across multiple submitters; uORF, upstream open reading frame; UTR, untranslated region.