TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27582	82969;82970;82971	chr2:178563388;178563387;178563386	chr2:179428115;179428114;179428113
N2AB	25941	78046;78047;78048	chr2:178563388;178563387;178563386	chr2:179428115;179428114;179428113
N2A	25014	75265;75266;75267	chr2:178563388;178563387;178563386	chr2:179428115;179428114;179428113
N2B	18517	55774;55775;55776	chr2:178563388;178563387;178563386	chr2:179428115;179428114;179428113
Novex-1	18642	56149;56150;56151	chr2:178563388;178563387;178563386	chr2:179428115;179428114;179428113
Novex-2	18709	56350;56351;56352	chr2:178563388;178563387;178563386	chr2:179428115;179428114;179428113
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-89
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.4639
• 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
T/A	rs1704394445	None	0.001	N	0.074	0.098	0.211220785272	gnomAD-4.0.0	3.18313E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85861E-06	1.43271E-05	0
T/I	None	None	0.655	N	0.465	0.148	0.362160248664	gnomAD-4.0.0	1.59157E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8586E-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
T/A	0.1116	likely_benign	0.1068	benign	-0.347	Destabilizing	0.001	N	0.074	neutral	N	0.476690894	None	None	N
T/C	0.32	likely_benign	0.3241	benign	-0.829	Destabilizing	0.983	D	0.352	neutral	None	None	None	None	N
T/D	0.7386	likely_pathogenic	0.7071	pathogenic	-1.791	Destabilizing	0.418	N	0.39	neutral	None	None	None	None	N
T/E	0.6134	likely_pathogenic	0.5911	pathogenic	-1.779	Destabilizing	0.129	N	0.406	neutral	None	None	None	None	N
T/F	0.2324	likely_benign	0.23	benign	-1.003	Destabilizing	0.836	D	0.467	neutral	None	None	None	None	N
T/G	0.3678	ambiguous	0.3332	benign	-0.513	Destabilizing	0.129	N	0.351	neutral	None	None	None	None	N
T/H	0.2741	likely_benign	0.2751	benign	-1.036	Destabilizing	0.002	N	0.311	neutral	None	None	None	None	N
T/I	0.1442	likely_benign	0.1404	benign	-0.005	Destabilizing	0.655	D	0.465	neutral	N	0.457024911	None	None	N
T/K	0.3093	likely_benign	0.2947	benign	-0.415	Destabilizing	0.002	N	0.177	neutral	None	None	None	None	N
T/L	0.1324	likely_benign	0.133	benign	-0.005	Destabilizing	0.418	N	0.419	neutral	None	None	None	None	N
T/M	0.1144	likely_benign	0.1086	benign	0.238	Stabilizing	0.94	D	0.372	neutral	None	None	None	None	N
T/N	0.2313	likely_benign	0.2125	benign	-0.828	Destabilizing	0.213	N	0.307	neutral	N	0.478926428	None	None	N
T/P	0.5234	ambiguous	0.5241	ambiguous	-0.091	Destabilizing	0.523	D	0.459	neutral	N	0.508533954	None	None	N
T/Q	0.3374	likely_benign	0.3218	benign	-1.16	Destabilizing	0.418	N	0.463	neutral	None	None	None	None	N
T/R	0.2581	likely_benign	0.2321	benign	-0.166	Destabilizing	0.264	N	0.405	neutral	None	None	None	None	N
T/S	0.1279	likely_benign	0.1201	benign	-0.745	Destabilizing	0.003	N	0.075	neutral	N	0.451987238	None	None	N
T/V	0.114	likely_benign	0.1164	benign	-0.091	Destabilizing	0.264	N	0.311	neutral	None	None	None	None	N
T/W	0.6376	likely_pathogenic	0.644	pathogenic	-1.134	Destabilizing	0.983	D	0.449	neutral	None	None	None	None	N
T/Y	0.2833	likely_benign	0.2859	benign	-0.663	Destabilizing	0.716	D	0.475	neutral	None	None	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.