TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14457	43594;43595;43596	chr2:178632637;178632636;178632635	chr2:179497364;179497363;179497362
N2AB	12816	38671;38672;38673	chr2:178632637;178632636;178632635	chr2:179497364;179497363;179497362
N2A	11889	35890;35891;35892	chr2:178632637;178632636;178632635	chr2:179497364;179497363;179497362
N2B	5392	16399;16400;16401	chr2:178632637;178632636;178632635	chr2:179497364;179497363;179497362
Novex-1	5517	16774;16775;16776	chr2:178632637;178632636;178632635	chr2:179497364;179497363;179497362
Novex-2	5584	16975;16976;16977	chr2:178632637;178632636;178632635	chr2:179497364;179497363;179497362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-95
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.5266
• 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
K/N	rs756061256	-0.178	0.116	N	0.395	0.105	0.241078983079	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/N	rs756061256	-0.178	0.116	N	0.395	0.105	0.241078983079	gnomAD-4.0.0	6.84311E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99599E-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
K/A	0.2529	likely_benign	0.2802	benign	-0.474	Destabilizing	0.001	N	0.283	neutral	None	None	None	None	N
K/C	0.6418	likely_pathogenic	0.6233	pathogenic	-0.397	Destabilizing	0.901	D	0.559	neutral	None	None	None	None	N
K/D	0.4751	ambiguous	0.5314	ambiguous	-0.046	Destabilizing	0.08	N	0.469	neutral	None	None	None	None	N
K/E	0.1189	likely_benign	0.1296	benign	0.042	Stabilizing	0.002	N	0.22	neutral	N	0.474924225	None	None	N
K/F	0.7358	likely_pathogenic	0.7448	pathogenic	-0.35	Destabilizing	0.749	D	0.591	neutral	None	None	None	None	N
K/G	0.3737	ambiguous	0.4043	ambiguous	-0.789	Destabilizing	0.08	N	0.518	neutral	None	None	None	None	N
K/H	0.2953	likely_benign	0.305	benign	-1.129	Destabilizing	0.596	D	0.477	neutral	None	None	None	None	N
K/I	0.2987	likely_benign	0.3103	benign	0.322	Stabilizing	0.08	N	0.561	neutral	None	None	None	None	N
K/L	0.3474	ambiguous	0.3666	ambiguous	0.322	Stabilizing	0.036	N	0.493	neutral	None	None	None	None	N
K/M	0.2065	likely_benign	0.2102	benign	0.122	Stabilizing	0.693	D	0.481	neutral	N	0.512114899	None	None	N
K/N	0.3056	likely_benign	0.3528	ambiguous	-0.197	Destabilizing	0.116	N	0.395	neutral	N	0.484957192	None	None	N
K/P	0.6174	likely_pathogenic	0.6695	pathogenic	0.086	Stabilizing	0.001	N	0.277	neutral	None	None	None	None	N
K/Q	0.1198	likely_benign	0.1202	benign	-0.238	Destabilizing	0.002	N	0.233	neutral	N	0.439894571	None	None	N
K/R	0.0872	likely_benign	0.0863	benign	-0.429	Destabilizing	0.061	N	0.409	neutral	N	0.48105065	None	None	N
K/S	0.2732	likely_benign	0.3136	benign	-0.768	Destabilizing	0.002	N	0.211	neutral	None	None	None	None	N
K/T	0.1167	likely_benign	0.1297	benign	-0.479	Destabilizing	0.002	N	0.281	neutral	N	0.490022264	None	None	N
K/V	0.2859	likely_benign	0.2981	benign	0.086	Stabilizing	0.002	N	0.353	neutral	None	None	None	None	N
K/W	0.7203	likely_pathogenic	0.701	pathogenic	-0.29	Destabilizing	0.972	D	0.547	neutral	None	None	None	None	N
K/Y	0.5863	likely_pathogenic	0.5891	pathogenic	0.005	Stabilizing	0.749	D	0.585	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.