TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28023	84292;84293;84294	chr2:178562065;178562064;178562063	chr2:179426792;179426791;179426790
N2AB	26382	79369;79370;79371	chr2:178562065;178562064;178562063	chr2:179426792;179426791;179426790
N2A	25455	76588;76589;76590	chr2:178562065;178562064;178562063	chr2:179426792;179426791;179426790
N2B	18958	57097;57098;57099	chr2:178562065;178562064;178562063	chr2:179426792;179426791;179426790
Novex-1	19083	57472;57473;57474	chr2:178562065;178562064;178562063	chr2:179426792;179426791;179426790
Novex-2	19150	57673;57674;57675	chr2:178562065;178562064;178562063	chr2:179426792;179426791;179426790
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-142
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.6023
• 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/R	None	None	0.698	N	0.491	0.261	0.339793275041	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
K/A	0.5208	ambiguous	0.591	pathogenic	-0.41	Destabilizing	0.754	D	0.52	neutral	None	None	None	None	N
K/C	0.7788	likely_pathogenic	0.8312	pathogenic	-0.576	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
K/D	0.7686	likely_pathogenic	0.8094	pathogenic	-0.103	Destabilizing	0.754	D	0.533	neutral	None	None	None	None	N
K/E	0.3439	ambiguous	0.4273	ambiguous	-0.04	Destabilizing	0.698	D	0.535	neutral	D	0.534366266	None	None	N
K/F	0.866	likely_pathogenic	0.8845	pathogenic	-0.359	Destabilizing	0.978	D	0.596	neutral	None	None	None	None	N
K/G	0.5991	likely_pathogenic	0.6585	pathogenic	-0.718	Destabilizing	0.754	D	0.553	neutral	None	None	None	None	N
K/H	0.4068	ambiguous	0.4437	ambiguous	-1.089	Destabilizing	0.978	D	0.533	neutral	None	None	None	None	N
K/I	0.5317	ambiguous	0.6069	pathogenic	0.358	Stabilizing	0.16	N	0.435	neutral	None	None	None	None	N
K/L	0.494	ambiguous	0.5443	ambiguous	0.358	Stabilizing	0.754	D	0.542	neutral	None	None	None	None	N
K/M	0.3685	ambiguous	0.4328	ambiguous	0.324	Stabilizing	0.97	D	0.533	neutral	N	0.519018138	None	None	N
K/N	0.6113	likely_pathogenic	0.6652	pathogenic	-0.251	Destabilizing	0.032	N	0.231	neutral	N	0.494620006	None	None	N
K/P	0.8054	likely_pathogenic	0.8145	pathogenic	0.133	Stabilizing	0.978	D	0.531	neutral	None	None	None	None	N
K/Q	0.2004	likely_benign	0.2275	benign	-0.463	Destabilizing	0.125	N	0.233	neutral	N	0.49259209	None	None	N
K/R	0.0791	likely_benign	0.0829	benign	-0.393	Destabilizing	0.698	D	0.491	neutral	N	0.488113901	None	None	N
K/S	0.5685	likely_pathogenic	0.633	pathogenic	-0.914	Destabilizing	0.754	D	0.477	neutral	None	None	None	None	N
K/T	0.2712	likely_benign	0.3275	benign	-0.667	Destabilizing	0.822	D	0.537	neutral	N	0.510817403	None	None	N
K/V	0.4879	ambiguous	0.5636	ambiguous	0.133	Stabilizing	0.754	D	0.533	neutral	None	None	None	None	N
K/W	0.8001	likely_pathogenic	0.8191	pathogenic	-0.218	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	N
K/Y	0.741	likely_pathogenic	0.7664	pathogenic	0.112	Stabilizing	0.978	D	0.565	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.