Mutated amino acid residues in deduced amyloid light-chain proteins
| VL subtype . | Germ line donor . | Mutated residue . | No. cases . | Replacement(s) . | Amino acid features . |
|---|---|---|---|---|---|
| VλI | 1c (n = 8) | Gln38 | 6 | His | Neutral to basic |
| Pro40 | 1 | Ser | Both neutral | ||
| Ser50 | 3 | Thr, Iso | All neutral | ||
| Arg | Neutral to basic | ||||
| VλII | 2a2 (n = 6) | Gln38 | 5 | His | Neutral to basic |
| Glu50 | 4 | Asp | Both are acidic | ||
| Ser52 | 4 | Asn (n = 2) | All neutral | ||
| Thr (n = 2) | |||||
| Ser94 | 1 | Asn | N-gly site | ||
| VλIII | 3r (n = 7) | Lys31b | 3 | Glu | Basic to acidic |
| 2 | Tyr, Asn | Basic to neutral | |||
| N-gly site | |||||
| Pro40 | 2 | Ala, Ser | All neutral | ||
| Ser52 | 6 | Thr (n = 3), | All neutral | ||
| Asn (n = 2) | |||||
| Asp | Neutral to acidic | ||||
| Ala90 | 3 | Thr (n = 2), | All neutral | ||
| Ser | |||||
| Ser94 | 4 | Gly (n = 2), Asn, | All neutral | ||
| Arg | Neutral to basic | ||||
| VλVI | 6a (n = 18) | Arg25 | 5 | Gly | Basic to neutral |
| Ser31a | 6 | Ala, Gly, Val, | All neutral | ||
| Asn (n = 2) | |||||
| Asp | Neutral to acidic | ||||
| Asn31b | 5 | Ser, Tyr (n = 2) | All neutral | ||
| Asp | Neutral to acidic | ||||
| Pro40 | 3 | Thr, Gly, Ser | All neutral | ||
| Ser43 | 8 | Ala (n = 8) | All neutral | ||
| Asn52 | 9 | Asp (n = 4) | Neutral to acidic | ||
| Lys | Neutral to basic | ||||
| Ser (n = 3), Thr | All neutral | ||||
| Gln53 | 5 | Val (n = 2) | Both neutral | ||
| Glu (n = 2) | Neutral to acidic | ||||
| Lys | Neutral to basic | ||||
| Ser93 | 12 | Asn (n = 4), Thr (n = 2), | All neutral | ||
| Gly (n = 4) | |||||
| Asp (n = 2) | Neutral to acidic | ||||
| Ser94 | 11 | Asn (n = 9), Gly | All neutral | ||
| Arg | Neutral to basic | ||||
| VKI | O18-O8 (n = 7) | Ser30 | 4 | Ala (n = 2), Thr, Asn | All neutral |
| Asn31 | 1 | Lys | Neutral to basic | ||
| Tyr32 | 3 | Phe (n = 2) | Both neutral | ||
| His | Neutral to basic | ||||
| Glu55 | 3 | Gln (n = 2) | Neutral to acidic | ||
| Lys | Acidic to basic | ||||
| Asp70 | 3 | Asn (n = 2) | Acidic to neutral, | ||
| N-gly sites | |||||
| His | Acidic to basic | ||||
| Thr72 | 2 | Iso | Both neutral | ||
| Asn | Neutral to basic, | ||||
| N-gly site | |||||
| Leu96 | 4 | Tyr, Pro, Thr, Phe | All neutral | ||
| LFVK431 (n = 4) | Gly28 | 3 | Asp (n = 3) | Neutral to acidic | |
| Tyr32 | 3 | Phe (n = 3) | Both neutral | ||
| Ala50 | 2 | Ser (n = 2) | Both neutral | ||
| Lys61 | 3 | Asn (n = 3) | All neutral, | ||
| N-gly sites | |||||
| Asp70 | 2 | His | Acidic to neutral | ||
| Asn | Acidic to neutral, | ||||
| N-gly site | |||||
| Ser93 | 1 | Asn | Both neutral | ||
| Arg96 | 3 | Tyr (n = 2), Pro | Basic to neutral |
| VL subtype . | Germ line donor . | Mutated residue . | No. cases . | Replacement(s) . | Amino acid features . |
|---|---|---|---|---|---|
| VλI | 1c (n = 8) | Gln38 | 6 | His | Neutral to basic |
| Pro40 | 1 | Ser | Both neutral | ||
| Ser50 | 3 | Thr, Iso | All neutral | ||
| Arg | Neutral to basic | ||||
| VλII | 2a2 (n = 6) | Gln38 | 5 | His | Neutral to basic |
| Glu50 | 4 | Asp | Both are acidic | ||
| Ser52 | 4 | Asn (n = 2) | All neutral | ||
| Thr (n = 2) | |||||
| Ser94 | 1 | Asn | N-gly site | ||
| VλIII | 3r (n = 7) | Lys31b | 3 | Glu | Basic to acidic |
| 2 | Tyr, Asn | Basic to neutral | |||
| N-gly site | |||||
| Pro40 | 2 | Ala, Ser | All neutral | ||
| Ser52 | 6 | Thr (n = 3), | All neutral | ||
| Asn (n = 2) | |||||
| Asp | Neutral to acidic | ||||
| Ala90 | 3 | Thr (n = 2), | All neutral | ||
| Ser | |||||
| Ser94 | 4 | Gly (n = 2), Asn, | All neutral | ||
| Arg | Neutral to basic | ||||
| VλVI | 6a (n = 18) | Arg25 | 5 | Gly | Basic to neutral |
| Ser31a | 6 | Ala, Gly, Val, | All neutral | ||
| Asn (n = 2) | |||||
| Asp | Neutral to acidic | ||||
| Asn31b | 5 | Ser, Tyr (n = 2) | All neutral | ||
| Asp | Neutral to acidic | ||||
| Pro40 | 3 | Thr, Gly, Ser | All neutral | ||
| Ser43 | 8 | Ala (n = 8) | All neutral | ||
| Asn52 | 9 | Asp (n = 4) | Neutral to acidic | ||
| Lys | Neutral to basic | ||||
| Ser (n = 3), Thr | All neutral | ||||
| Gln53 | 5 | Val (n = 2) | Both neutral | ||
| Glu (n = 2) | Neutral to acidic | ||||
| Lys | Neutral to basic | ||||
| Ser93 | 12 | Asn (n = 4), Thr (n = 2), | All neutral | ||
| Gly (n = 4) | |||||
| Asp (n = 2) | Neutral to acidic | ||||
| Ser94 | 11 | Asn (n = 9), Gly | All neutral | ||
| Arg | Neutral to basic | ||||
| VKI | O18-O8 (n = 7) | Ser30 | 4 | Ala (n = 2), Thr, Asn | All neutral |
| Asn31 | 1 | Lys | Neutral to basic | ||
| Tyr32 | 3 | Phe (n = 2) | Both neutral | ||
| His | Neutral to basic | ||||
| Glu55 | 3 | Gln (n = 2) | Neutral to acidic | ||
| Lys | Acidic to basic | ||||
| Asp70 | 3 | Asn (n = 2) | Acidic to neutral, | ||
| N-gly sites | |||||
| His | Acidic to basic | ||||
| Thr72 | 2 | Iso | Both neutral | ||
| Asn | Neutral to basic, | ||||
| N-gly site | |||||
| Leu96 | 4 | Tyr, Pro, Thr, Phe | All neutral | ||
| LFVK431 (n = 4) | Gly28 | 3 | Asp (n = 3) | Neutral to acidic | |
| Tyr32 | 3 | Phe (n = 3) | Both neutral | ||
| Ala50 | 2 | Ser (n = 2) | Both neutral | ||
| Lys61 | 3 | Asn (n = 3) | All neutral, | ||
| N-gly sites | |||||
| Asp70 | 2 | His | Acidic to neutral | ||
| Asn | Acidic to neutral, | ||||
| N-gly site | |||||
| Ser93 | 1 | Asn | Both neutral | ||
| Arg96 | 3 | Tyr (n = 2), Pro | Basic to neutral |
These represent the most commonly mutated residues found in our sample with particular focus on amyloid-associated light-chain residues as described in references 8 and 30. Residues in bold are in complementarity-determining regions (CDR). N-gly site indicates the N-glycosylation site.