TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5626	17101;17102;17103	chr2:178732093;178732092;178732091	chr2:179596820;179596819;179596818
N2AB	5309	16150;16151;16152	chr2:178732093;178732092;178732091	chr2:179596820;179596819;179596818
N2A	4382	13369;13370;13371	chr2:178732093;178732092;178732091	chr2:179596820;179596819;179596818
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-39
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.5322
• 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
H/D	rs1226327061	-0.001	0.302	N	0.401	0.234	0.337621943819	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
H/D	rs1226327061	-0.001	0.302	N	0.401	0.234	0.337621943819	gnomAD-4.0.0	3.42588E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50297E-06	0	0
H/Y	None	None	0.866	N	0.423	0.159	0.353548585375	gnomAD-4.0.0	6.85176E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00594E-07	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
H/A	0.1918	likely_benign	0.1962	benign	0.124	Stabilizing	0.051	N	0.369	neutral	None	None	None	None	N
H/C	0.1413	likely_benign	0.1376	benign	0.908	Stabilizing	0.004	N	0.363	neutral	None	None	None	None	N
H/D	0.1751	likely_benign	0.1785	benign	-0.073	Destabilizing	0.302	N	0.401	neutral	N	0.446227206	None	None	N
H/E	0.2428	likely_benign	0.2438	benign	-0.011	Destabilizing	0.365	N	0.295	neutral	None	None	None	None	N
H/F	0.2168	likely_benign	0.2285	benign	1.054	Stabilizing	0.582	D	0.461	neutral	None	None	None	None	N
H/G	0.2219	likely_benign	0.2304	benign	-0.219	Destabilizing	0.2	N	0.38	neutral	None	None	None	None	N
H/I	0.1874	likely_benign	0.188	benign	1.036	Stabilizing	0.002	N	0.378	neutral	None	None	None	None	N
H/K	0.2008	likely_benign	0.1899	benign	0.305	Stabilizing	0.111	N	0.334	neutral	None	None	None	None	N
H/L	0.1039	likely_benign	0.1055	benign	1.036	Stabilizing	0.086	N	0.383	neutral	N	0.455193406	None	None	N
H/M	0.3586	ambiguous	0.3608	ambiguous	0.814	Stabilizing	0.83	D	0.503	neutral	None	None	None	None	N
H/N	0.0819	likely_benign	0.0875	benign	0.324	Stabilizing	0.302	N	0.342	neutral	N	0.435183494	None	None	N
H/P	0.3881	ambiguous	0.4135	ambiguous	0.757	Stabilizing	0.68	D	0.501	neutral	N	0.505910228	None	None	N
H/Q	0.1328	likely_benign	0.132	benign	0.491	Stabilizing	0.512	D	0.373	neutral	N	0.420214041	None	None	N
H/R	0.0792	likely_benign	0.0754	benign	-0.418	Destabilizing	None	N	0.125	neutral	N	0.39612646	None	None	N
H/S	0.1321	likely_benign	0.1313	benign	0.441	Stabilizing	0.022	N	0.214	neutral	None	None	None	None	N
H/T	0.1484	likely_benign	0.141	benign	0.608	Stabilizing	0.008	N	0.286	neutral	None	None	None	None	N
H/V	0.1665	likely_benign	0.1654	benign	0.757	Stabilizing	0.111	N	0.377	neutral	None	None	None	None	N
H/W	0.3599	ambiguous	0.3403	ambiguous	1.144	Stabilizing	0.991	D	0.459	neutral	None	None	None	None	N
H/Y	0.0835	likely_benign	0.0865	benign	1.356	Stabilizing	0.866	D	0.423	neutral	N	0.457868352	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.