TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14701	44326;44327;44328	chr2:178630857;178630856;178630855	chr2:179495584;179495583;179495582
N2AB	13060	39403;39404;39405	chr2:178630857;178630856;178630855	chr2:179495584;179495583;179495582
N2A	12133	36622;36623;36624	chr2:178630857;178630856;178630855	chr2:179495584;179495583;179495582
N2B	5636	17131;17132;17133	chr2:178630857;178630856;178630855	chr2:179495584;179495583;179495582
Novex-1	5761	17506;17507;17508	chr2:178630857;178630856;178630855	chr2:179495584;179495583;179495582
Novex-2	5828	17707;17708;17709	chr2:178630857;178630856;178630855	chr2:179495584;179495583;179495582
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-98
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.4476
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
D/A	rs1286396788	None	0.012	N	0.267	0.135	0.178374595973	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/A	rs1286396788	None	0.012	N	0.267	0.135	0.178374595973	gnomAD-4.0.0	6.57341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47046E-05	0	0
D/G	None	None	0.058	N	0.276	0.146	0.154104182512	gnomAD-4.0.0	1.5922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
D/A	0.1193	likely_benign	0.1205	benign	-0.226	Destabilizing	0.012	N	0.267	neutral	N	0.432743017	None	None	N
D/C	0.5712	likely_pathogenic	0.5446	ambiguous	0.093	Stabilizing	0.869	D	0.495	neutral	None	None	None	None	N
D/E	0.088	likely_benign	0.0823	benign	-0.352	Destabilizing	None	N	0.113	neutral	N	0.395282638	None	None	N
D/F	0.5675	likely_pathogenic	0.5522	ambiguous	-0.249	Destabilizing	0.637	D	0.444	neutral	None	None	None	None	N
D/G	0.127	likely_benign	0.121	benign	-0.417	Destabilizing	0.058	N	0.276	neutral	N	0.43335908	None	None	N
D/H	0.2705	likely_benign	0.2587	benign	-0.132	Destabilizing	0.303	N	0.351	neutral	N	0.447175988	None	None	N
D/I	0.2931	likely_benign	0.3023	benign	0.226	Stabilizing	0.366	N	0.547	neutral	None	None	None	None	N
D/K	0.1918	likely_benign	0.2158	benign	0.339	Stabilizing	0.016	N	0.271	neutral	None	None	None	None	N
D/L	0.3167	likely_benign	0.3316	benign	0.226	Stabilizing	0.075	N	0.417	neutral	None	None	None	None	N
D/M	0.49	ambiguous	0.4979	ambiguous	0.36	Stabilizing	0.869	D	0.417	neutral	None	None	None	None	N
D/N	0.1048	likely_benign	0.0944	benign	0.092	Stabilizing	0.058	N	0.331	neutral	N	0.445227066	None	None	N
D/P	0.4177	ambiguous	0.4806	ambiguous	0.097	Stabilizing	0.366	N	0.426	neutral	None	None	None	None	N
D/Q	0.2243	likely_benign	0.241	benign	0.107	Stabilizing	0.039	N	0.327	neutral	None	None	None	None	N
D/R	0.2829	likely_benign	0.2953	benign	0.464	Stabilizing	0.001	N	0.188	neutral	None	None	None	None	N
D/S	0.1154	likely_benign	0.1101	benign	-0.015	Destabilizing	0.003	N	0.236	neutral	None	None	None	None	N
D/T	0.1844	likely_benign	0.1916	benign	0.129	Stabilizing	0.039	N	0.327	neutral	None	None	None	None	N
D/V	0.1734	likely_benign	0.1776	benign	0.097	Stabilizing	0.177	N	0.464	neutral	N	0.436253628	None	None	N
D/W	0.8139	likely_pathogenic	0.8079	pathogenic	-0.15	Destabilizing	0.869	D	0.543	neutral	None	None	None	None	N
D/Y	0.2062	likely_benign	0.1938	benign	-0.016	Destabilizing	0.57	D	0.446	neutral	N	0.447704949	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.