Summary of FGA variants associated with renal amyloidosis
| Aα-chain frameshift variants associated with renal amyloidosis . | FGA nucleotide variations . | Predicted C-terminal mutant Aα-chains encoded by the respective shifted reading frames with premature stop at codon 548 . | Renal Aα-chain fibril composition . |
|---|---|---|---|
| Met517_Phe521delinsGlnSerfs*28 (p. Met536_Phe540delinsGlnSerfs*28)10 | c.1606_1620 delATGTTAGGAGAGTTT insCA | …QSVRLSLGAQNLASSQIQRNPVLITLG | No |
| Phe521Leufs*28 (p.Phe540Leufs*28) (New variant reported here) | c.1620delT | …LSVRLSLGAQNLASSQIQRNPVLITLG | Yes (this report) |
| Phe521Serfs*27 (p.Phe540Ser*27)9 | c.1619_1622delTTGT | …SVRLSLGAQNLASSQIQRNPVLITLG | Yes |
| Val522Alafs*27 (p.Val541Alafs*27)4 | c.1622delT | …AVRLSLGAQNLASSQIQRNPVLITLG | Yes (our previous AFib kindred) |
| Ser523Argfs*26 (p.Ser543Argfs*26)13 | c.1624_1627del AGTG | …RLSLGAQNLASSQIQRNPVLITLG | Yes |
| Glu524Glufs*25 (p.Glu543Glufs*25)11 | c.1629delG | …LSLGAQNLASSQIQRNPVLITLG | No |
| Thr525Thrfs*24 (p.Thr544Thrfs*24)3 | c.1632delT | …SLGAQNLASSQIQRNPVLITLG | Yes |
| Ser532Serfs*16 (p.Ser551Serfs*16)9 | c.1653delT | …ASSQIQRNPVLITLG | No |
| Aα-chain frameshift variants associated with renal amyloidosis . | FGA nucleotide variations . | Predicted C-terminal mutant Aα-chains encoded by the respective shifted reading frames with premature stop at codon 548 . | Renal Aα-chain fibril composition . |
|---|---|---|---|
| Met517_Phe521delinsGlnSerfs*28 (p. Met536_Phe540delinsGlnSerfs*28)10 | c.1606_1620 delATGTTAGGAGAGTTT insCA | …QSVRLSLGAQNLASSQIQRNPVLITLG | No |
| Phe521Leufs*28 (p.Phe540Leufs*28) (New variant reported here) | c.1620delT | …LSVRLSLGAQNLASSQIQRNPVLITLG | Yes (this report) |
| Phe521Serfs*27 (p.Phe540Ser*27)9 | c.1619_1622delTTGT | …SVRLSLGAQNLASSQIQRNPVLITLG | Yes |
| Val522Alafs*27 (p.Val541Alafs*27)4 | c.1622delT | …AVRLSLGAQNLASSQIQRNPVLITLG | Yes (our previous AFib kindred) |
| Ser523Argfs*26 (p.Ser543Argfs*26)13 | c.1624_1627del AGTG | …RLSLGAQNLASSQIQRNPVLITLG | Yes |
| Glu524Glufs*25 (p.Glu543Glufs*25)11 | c.1629delG | …LSLGAQNLASSQIQRNPVLITLG | No |
| Thr525Thrfs*24 (p.Thr544Thrfs*24)3 | c.1632delT | …SLGAQNLASSQIQRNPVLITLG | Yes |
| Ser532Serfs*16 (p.Ser551Serfs*16)9 | c.1653delT | …ASSQIQRNPVLITLG | No |
Irrespective of the nucleotide position of the FGA deletion/insertion anomalies, all frameshifts truncate at codon 548 and generate similar mutant C-terminal sequences. In the third column of the table are shown the predicted C-terminal portions of frameshifts: in bold are the portions that differ in 4/5 residues between frameshifts and in nonbold is the common 15-amino-acid sequence shared by all frameshifts: ASSQIQRNPVLITLG contains the VLITL motif (underlined). All amyloidogenic Aα-chain frameshift variants are listed according to the 2 nomenclatures. To convert the conventional mature protein amino acid numbering to the HGVS nomenclature, add 19 nucleotides for Aα-chain changes.