TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16371	49336;49337;49338	chr2:178614286;178614285;178614284	chr2:179479013;179479012;179479011
N2AB	14730	44413;44414;44415	chr2:178614286;178614285;178614284	chr2:179479013;179479012;179479011
N2A	13803	41632;41633;41634	chr2:178614286;178614285;178614284	chr2:179479013;179479012;179479011
N2B	7306	22141;22142;22143	chr2:178614286;178614285;178614284	chr2:179479013;179479012;179479011
Novex-1	7431	22516;22517;22518	chr2:178614286;178614285;178614284	chr2:179479013;179479012;179479011
Novex-2	7498	22717;22718;22719	chr2:178614286;178614285;178614284	chr2:179479013;179479012;179479011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-6
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2597
• 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/I	None	None	0.994	N	0.609	0.418	0.596538173739	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/R	None	None	0.994	N	0.654	0.456	0.671773944551	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	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	0.0952	likely_benign	0.0937	benign	-1.131	Destabilizing	0.122	N	0.235	neutral	N	0.444831641	None	None	N
T/C	0.3802	ambiguous	0.3437	ambiguous	-0.694	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
T/D	0.6487	likely_pathogenic	0.6253	pathogenic	-1.526	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
T/E	0.452	ambiguous	0.4466	ambiguous	-1.298	Destabilizing	0.985	D	0.555	neutral	None	None	None	None	N
T/F	0.2701	likely_benign	0.2582	benign	-0.845	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
T/G	0.332	likely_benign	0.3206	benign	-1.554	Destabilizing	0.942	D	0.561	neutral	None	None	None	None	N
T/H	0.2279	likely_benign	0.2131	benign	-1.682	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
T/I	0.1943	likely_benign	0.187	benign	-0.008	Destabilizing	0.994	D	0.609	neutral	N	0.470160018	None	None	N
T/K	0.2022	likely_benign	0.1868	benign	-0.278	Destabilizing	0.961	D	0.573	neutral	N	0.469398168	None	None	N
T/L	0.1159	likely_benign	0.1102	benign	-0.008	Destabilizing	0.97	D	0.477	neutral	None	None	None	None	N
T/M	0.0985	likely_benign	0.1005	benign	-0.112	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/N	0.1569	likely_benign	0.1445	benign	-1.068	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
T/P	0.8496	likely_pathogenic	0.8532	pathogenic	-0.352	Destabilizing	0.994	D	0.603	neutral	D	0.632542723	None	None	N
T/Q	0.2155	likely_benign	0.2107	benign	-0.774	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
T/R	0.1782	likely_benign	0.1665	benign	-0.613	Destabilizing	0.994	D	0.654	neutral	N	0.466725835	None	None	N
T/S	0.1053	likely_benign	0.1009	benign	-1.27	Destabilizing	0.835	D	0.499	neutral	N	0.400431936	None	None	N
T/V	0.1576	likely_benign	0.145	benign	-0.352	Destabilizing	0.97	D	0.459	neutral	None	None	None	None	N
T/W	0.6698	likely_pathogenic	0.6654	pathogenic	-1.06	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/Y	0.3193	likely_benign	0.3071	benign	-0.626	Destabilizing	0.999	D	0.747	deleterious	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.