TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1599	5020;5021;5022	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893
N2AB	1599	5020;5021;5022	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893
N2A	1599	5020;5021;5022	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893
N2B	1553	4882;4883;4884	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893
Novex-1	1553	4882;4883;4884	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893
Novex-2	1553	4882;4883;4884	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893
Novex-3	1599	5020;5021;5022	chr2:178777168;178777167;178777166	chr2:179641895;179641894;179641893

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-7
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2944
• 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/Y	rs757510119	0.851	0.997	N	0.455	0.425	0.198526703765	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
H/Y	rs757510119	0.851	0.997	N	0.455	0.425	0.198526703765	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
H/Y	rs757510119	0.851	0.997	N	0.455	0.425	0.198526703765	gnomAD-4.0.0	2.56127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78386E-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
H/A	0.4799	ambiguous	0.4269	ambiguous	0.518	Stabilizing	0.985	D	0.496	neutral	None	None	None	None	N
H/C	0.461	ambiguous	0.3712	ambiguous	0.629	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
H/D	0.5073	ambiguous	0.445	ambiguous	-0.283	Destabilizing	0.98	D	0.49	neutral	N	0.423973043	None	None	N
H/E	0.5384	ambiguous	0.4741	ambiguous	-0.276	Destabilizing	0.931	D	0.451	neutral	None	None	None	None	N
H/F	0.4982	ambiguous	0.4559	ambiguous	1.043	Stabilizing	0.999	D	0.548	neutral	None	None	None	None	N
H/G	0.5062	ambiguous	0.4409	ambiguous	0.3	Stabilizing	0.993	D	0.523	neutral	None	None	None	None	N
H/I	0.6082	likely_pathogenic	0.5306	ambiguous	1.055	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	N
H/K	0.6206	likely_pathogenic	0.5542	ambiguous	0.406	Stabilizing	0.971	D	0.457	neutral	None	None	None	None	N
H/L	0.2848	likely_benign	0.2406	benign	1.055	Stabilizing	0.99	D	0.543	neutral	N	0.445614473	None	None	N
H/M	0.7012	likely_pathogenic	0.6332	pathogenic	0.668	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
H/N	0.1816	likely_benign	0.157	benign	0.234	Stabilizing	0.99	D	0.429	neutral	N	0.442489716	None	None	N
H/P	0.2855	likely_benign	0.2489	benign	0.899	Stabilizing	0.999	D	0.614	neutral	N	0.445375115	None	None	N
H/Q	0.3234	likely_benign	0.2887	benign	0.303	Stabilizing	0.659	D	0.215	neutral	N	0.447222146	None	None	N
H/R	0.3364	likely_benign	0.2922	benign	-0.101	Destabilizing	0.98	D	0.451	neutral	N	0.448416598	None	None	N
H/S	0.3397	likely_benign	0.2874	benign	0.413	Stabilizing	0.985	D	0.45	neutral	None	None	None	None	N
H/T	0.5159	ambiguous	0.4518	ambiguous	0.511	Stabilizing	0.998	D	0.523	neutral	None	None	None	None	N
H/V	0.5274	ambiguous	0.4553	ambiguous	0.899	Stabilizing	0.998	D	0.567	neutral	None	None	None	None	N
H/W	0.5612	ambiguous	0.5017	ambiguous	0.913	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
H/Y	0.1674	likely_benign	0.1477	benign	1.175	Stabilizing	0.997	D	0.455	neutral	N	0.446903631	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.