Table 2.
ARSB sequence variants identified in more than one independent family
| Exon/Intron | Nucleotide Change | Predicted Amino Acid Change | Number of Reports | Clinical Significance | Variant Identifier (ClinVar ID and/or dbSNP Number, if Available) |
|---|---|---|---|---|---|
| Exon 1 | c.157G>A | p.(Asp53Asn) | 6 | Likely pathogenic | |
| Exon 1 | c.160G>A | p.(Asp54Asn) | 5 | Likely pathogenic | |
| Exon 1 | c.171G>C | p.(Trp57Cys) | 2 | Uncertain significance | |
| Exon 1 | c.175G>A | p.(Asp59Asn) | 2 | Uncertain significance | |
| Exon 1 | c.215T>G | p.(Leu72Arg) | 13 | Likely pathogenic | |
| Exon 1 | c.238del | p.(Val80Cysfs*34) | 6 | Pathogenic | ClinVar Allele ID: 15920; rs750845916 |
| Exon 1 | c.245del | p.(Leu82Argfs*32) | 2 | Likely pathogenic | |
| Exon 1 | c.245T>G | p.(Leu82Arg) | 3 | Likely pathogenic | rs750845916 |
| Exon 1 | c.262C>T | p.(Gln88*) | 4 | Pathogenic | |
| Exon 1 | c.275C>A | p.(Thr92Lys) | 9 | Uncertain significance | |
| Exon 1 | c.275C>T | p.(Thr92Met) | 2 | Uncertain significance | |
| Exon 1 | c.284G>A | p.(Arg95Gln) | 6 | Likely pathogenic | ClinVar Allele ID: 15923 |
| Exon 1 | c.289C>T | p.(Gln97*) | 4 | Likely pathogenic | |
| Exon 1 | c.293T>A | p.(Leu98Gln) | 4 | Likely pathogenic | |
| Exon 1 | c.293T>C | p.(Leu98Pro) | 2 | Uncertain significance | |
| Exon 1 | c.293T>G | p.(Leu98Arg) | 8 | Likely pathogenic | |
| Exon 1 | c.305G>A | p.(Arg102His) | 2 | Uncertain significance | |
| Exon 1 | c.312G>C | p.(Gln104His) | 4 | Uncertain significance | rs150087888 |
| Exon 2 | c.332A>C | p.(His111Pro) | 5 | Uncertain significance | rs775780931 |
| Exon 2 | c.349T>C | p.(Cys117Arg) | 6 | Likely pathogenic | ClinVar Allele ID: 15917 |
| Exon 2 | c.384_386del | p.(Leu129del) | 3 | Uncertain significance | ClinVar Allele ID: 106583 |
| Exon 2 | c.395T>C | p.(Leu132Pro) | 3 | Likely pathogenic | |
| Exon 2 | c.427del | p.(Val143Serfs*41) | 12 | Pathogenic | rs746206847 |
| Exon 2 | c.430G>A | p.(Gly144Arg) | 8 | Likely pathogenic | |
| Exon 2 | c.437G>C | p.(Trp146Ser) | 2 | Uncertain significance | |
| Exon 2 | c.438G>A | p.(Trp146*) | 4 | Likely pathogenic | |
| Exon 2 | c.440A>C | p.(His147Pro) | 2 | Uncertain significance | |
| Exon 2 | c.454C>T | p.(Arg152Trp) | 62 | Pathogenic | |
| Exon 2 | c.464G>A | p.(Cys155Tyr) | 3 | Uncertain significance | |
| Exon 2 | c.478C>T | p.(Arg160*) | 16 | Pathogenic | |
| Exon 2 | c.479G>A | p.(Arg160Gln) | 13 | Likely pathogenic | |
| Exon 2 | c.499G>A | p.(Gly167Arg) | 5 | Uncertain significance | |
| Exon 3 | c.511G>A | p.(Gly171Ser) | 3 | Likely pathogenic | |
| Exon 3 | c.533A>T | p.(His178Leu) | 29 | Likely pathogenic | |
| Exon 3 | c.571C>T | p.(Arg191*) | 7 | Pathogenic | |
| Exon 3 | c.574T>C | p.(Cys192Arg) | 15 | Likely pathogenic | |
| Exon 3 | c.589C>T | p.(Arg197*) | 5 | Pathogenic | rs118203943 |
| Exon 3 | c.629A>G | p.(Tyr210Cys) | 46 | Pathogenic | ClinVar Allele ID: 15924 |
| Intron 3 | c.691‐1G>A | — | 3 | Likely pathogenic | rs6870443 |
| Exon 4 | c.707T>C | p.(Leu236Pro) | 2 | Uncertain significance | ClinVar Allele ID: 15918 |
| Exon 4 | c.710C>A | p.(Ala237Asp) | 4 | Likely benign | |
| Exon 4 | c.716A>G | p.(Gln239Arg) | 3 | Uncertain significance | |
| Exon 4 | c.753C>G | p.(Tyr251*) | 43 | Pathogenic | |
| Exon 4 | c.765T>A | p.(Tyr255*) | 3 | Likely pathogenic | rs749015246 |
| Exon 4 | c.797A>C | p.(Tyr266Ser) | 7 | Uncertain significance | |
| Exon 5a | c.(898+1_899‐1)_(1142+1_1143‐1)del | — | 6 | Pathogenic | |
| Exon 5 | c.899‐1341_1142+1051del | — | 1 | Pathogenic | |
| Exon 5 | c.903C>G | p.(Asn301Lys) | 4 | Likely pathogenic | rs779378413 |
| Exon 5 | c.904G>A | p.(Gly302Arg) | 10 | Uncertain significance | |
| Exon 5 | c.908G>A | p.(Gly303Glu) | 5 | Likely pathogenic | |
| Exon 5 | c.937C>G | p.(Pro313Ala) | 11 | Likely pathogenic | |
| Exon 5 | c.943C>T | p.(Arg315*) | 10 | Likely pathogenic | rs727503809 |
| Exon 5 | c.944G>A | p.(Arg315Gln) | 22 | Likely pathogenic | ClinVar Allele ID: 177363 |
| Exon 5 | c.960C>G | p.(Ser320Arg) | 3 | Uncertain significance | |
| Exon 5 | c.962T>C | p.(Leu321Pro) | 60 | Pathogenic | |
| Exon 5 | c.966G>A | p.(Trp322*) | 2 | Pathogenic | rs398123125 |
| Exon 5 | c.971G>T | p.(Gly324Val) | 5 | Likely pathogenic | ClinVar Allele ID: 98267; rs773492223 |
| Exon 5 | c.979C>T | p.(Arg327*) | 16 | Pathogenic | rs201168448 |
| Exon 5 | c.1001G>T | p.(Ser334Ile) | 3 | Uncertain significance | |
| Exon 5 | c.1036del | p.(Glu346Serfs*11) | 13 | Pathogenic | |
| Exon 5 | c.1057T>A | p.(Trp353Arg) | 2 | Uncertain significance | |
| Exon 5 | c.1079T>C | p.(Leu360Pro) | 6 | Likely pathogenic | |
| Exon 5 | c.1127T>A | p.(Val376Glu) | 4 | Likely pathogenic | |
| Exon 5 | c.1142+2T>A | — | 2 | Likely pathogenic | |
| Exon 5 | c.1142+2T>C | — | 4 | Pathogenic | |
| Intron 5 | c.1143‐1G>C | — | 16 | Pathogenic | ClinVar Allele ID: 15926 |
| Intron 5 | c.1143‐8T>G | — | 24 | Likely pathogenic | ClinVar Allele ID: 15927; rs431905496 |
| Exon 6 | c.1151G>A | p.(Ser384Asn) | 9 | Benign | ClinVar Allele ID: 98263; rs25414 |
| Exon 6 | c.1168G>A | p.(Glu390Lys) | 6 | Likely pathogenic | |
| Exon 6 | c.1178A>C | p.(His393Pro) | 10 | Uncertain significance | ClinVar Allele ID: 15925 |
| Exon 6 | c.1178A>G | p.(His393Arg) | 3 | Uncertain significance | |
| Exon 6 | c.1197C>G | p.(Phe399Leu) | 17 | Likely pathogenic | rs200793396 |
| Intron 6 | c.1213+5G>A | — | 2 | Uncertain significance | |
| Intron 6 | c.1213+6T>C | — | 3 | Pathogenic | |
| Exon 7 | c.1214G>A | p.(Cys405Tyr) | 3 | Uncertain significance | ClinVar Allele ID: 15919; rs118203941 |
| Exon 7 | c.1289A>G | p.(His430Arg) | 3 | Likely pathogenic | |
| Exon 7 | c.1325C>T | p.(Thr442Met) | 3 | Uncertain significance | ClinVar Allele ID: 368534 |
| Exon 7 | c.1336G>A | p.(Gly446Ser) | 3 | Uncertain significance | |
| Intron 7 | c.1336+2T>G | — | 7 | Pathogenic | rs768012515 |
| Exon 8 | c.1340G>T | p.(Cys447Phe) | 4 | Uncertain significance | |
| Exon 8 | c.1350G>C | p.(Trp450Cys) | 11 | Likely pathogenic | rs555785323 |
| Exon 8 | c.1366C>T | p.(Gln456*) | 4 | Pathogenic | rs200188234 |
| Exon 8 | c.1415T>C | p. (Leu472Pro) | 2 | Likely pathogenic | |
| Exon 8 | c.1450A>G | p.(Arg484Gly) | 2 | Uncertain significance | ClinVar Allele ID: 187113 |
| Exon 8 | c.1457A>T | p.(Asp486Val) | 6 | Uncertain significance | |
| Exon 8 | c.1534_1556del | p.(Val512Profs*3) | 13 | Uncertain significance | |
| Exon 8 | c.1562G>A | p.(Cys521Tyr) | 9 | Uncertain significance | |
| Exon 8 | c.1577del | p.(Thr526Metfs*48) | 8 | Pathogenic | |
| Exon 8 | c.1582_1596del | p.(Val528_Trp532del) | 2 | Uncertain significance |
Variants classified per Richards et al. (2015). ClinVar accessed 06/05/2017.
a
Deletion of exon 5 without defined boundaries.