Table 1.
Molecular data of individuals with SRSF1 variants
| Subjects | Genomic changeg | Coding changeh | Protein change | Variant type | Inheritance | Polyphen-2 score | Varsome predictiona,b,c,d,e,f |
|---|---|---|---|---|---|---|---|
| I1 | g.56083708_56083709del | c.377_378del | p.Ser126Trpfs∗17 | Frameshift | Not inherited from the mother | – | Pathogenic: PVS1 PM2 PS2 |
| I2, I3, I4 | g.56083236C>T | c.478G>A | p.Val160Met | Missense | De novo | Probably damaging 0.999 | Likely pathogenic: PS2 PM2 PP3 |
| I5 | g.56082937dup | c.579dup | p.Val194Serfs∗2 | Frameshift | De novo | – | Pathogenic: PVS1 PM2 PS2 |
| I6 | g.55806534_56540597del | Not applicable | Not applicable | Deletion | De novo | – | – |
| I7 | g.56084417G>A | c.82C>T | p.Arg28∗ | Nonsense | De novo | – | Pathogenic: PVS1 PM2 PS2 |
| I8 | g.56083166T>C | c.548A>G | p.His183Arg | Missense | De novo | Probably damaging 1 | Likely pathogenic: PS2 PM2 PP3 |
| I9 | g.56084380C>A | c.119G>T | p.Gly40Val | Missense | De novo | Probably damaging 1 | Likely pathogenic: PS2 PM2 PP3 |
| I10 | g.56084402C>A | c.97G>T | p.Glu33∗ | Nonsense | De novo | – | Pathogenic: PVS1 PM2 PS2 |
| I11 | g.56082914del | c.601del | p.Ser201Valfs∗87 | Frameshift | De novo | – | Pathogenic: PVS1 PM2 PS2 |
| I12 | g.56083875C>T | c.208G>A | p.Ala70Thr | Missense | De novo | Probably damaging 1 | Likely pathogenic: PS2 PM2 PP3 |
| I13 | g.56084428G>A | c.71C>T | p.Pro24Leu | Missense | De novo | Probably damaging 1 | Likely pathogenic: PP3 PM2 PP2 PS2 |
| I14 | g.56083852A>C | c.231T>G | p.Tyr77∗ | Nonsense | De novo | – | Pathogenic: PVS1 PM2 PS2 |
| I15 | g.56083832A>C | c.251T>G | p.Leu84Arg | Missense | De novo | Probably damaging 1 | Likely pathogenic: PS2 PM2 PP3 |
| I16 | g.56084369C>T | c.130G>A | p.Asp44Asn | Missense | De novo | Benign 0.029 | Uncertain significance: PP2 PM2 PS2 BP4 |
| I17 | g.55442363_56309063del | Not applicable | Not applicable | Deletion | De novo | – | – |
a
PVS1, predicted loss-of-function variant.
b
PS2, de novo (both maternity and paternity confirmed) in an individual with the disease and no family history.
c
PM2, absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.
d
PP2, missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
e
PP3, multiple lines of computational evidence support a deleterious effect on the gene or gene product.
f
BP4, multiple lines of computational evidence suggest no impact on gene or gene product.
g
GenBank: NC_000017.10
h
GenBank: NM_006924.5