TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17136	51631;51632;51633	chr2:178610120;178610119;178610118	chr2:179474847;179474846;179474845
N2AB	15495	46708;46709;46710	chr2:178610120;178610119;178610118	chr2:179474847;179474846;179474845
N2A	14568	43927;43928;43929	chr2:178610120;178610119;178610118	chr2:179474847;179474846;179474845
N2B	8071	24436;24437;24438	chr2:178610120;178610119;178610118	chr2:179474847;179474846;179474845
Novex-1	8196	24811;24812;24813	chr2:178610120;178610119;178610118	chr2:179474847;179474846;179474845
Novex-2	8263	25012;25013;25014	chr2:178610120;178610119;178610118	chr2:179474847;179474846;179474845
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-12
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.8632
• 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	None	None	0.651	N	0.413	0.12	0.17258766438	gnomAD-4.0.0	1.59321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86159E-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	0.3558	ambiguous	0.455	ambiguous	0.018	Stabilizing	0.505	D	0.455	neutral	None	None	None	None	N
K/C	0.6927	likely_pathogenic	0.7599	pathogenic	-0.494	Destabilizing	0.995	D	0.538	neutral	None	None	None	None	N
K/D	0.526	ambiguous	0.6491	pathogenic	-0.351	Destabilizing	0.834	D	0.534	neutral	None	None	None	None	N
K/E	0.199	likely_benign	0.2854	benign	-0.356	Destabilizing	0.435	N	0.523	neutral	N	0.429856953	None	None	N
K/F	0.8581	likely_pathogenic	0.9124	pathogenic	-0.306	Destabilizing	0.982	D	0.55	neutral	None	None	None	None	N
K/G	0.4076	ambiguous	0.5066	ambiguous	-0.114	Destabilizing	0.834	D	0.571	neutral	None	None	None	None	N
K/H	0.3175	likely_benign	0.3841	ambiguous	-0.174	Destabilizing	0.946	D	0.463	neutral	None	None	None	None	N
K/I	0.4945	ambiguous	0.5944	pathogenic	0.285	Stabilizing	0.93	D	0.618	neutral	N	0.489825189	None	None	N
K/L	0.431	ambiguous	0.5178	ambiguous	0.285	Stabilizing	0.712	D	0.571	neutral	None	None	None	None	N
K/M	0.3622	ambiguous	0.4519	ambiguous	-0.168	Destabilizing	0.982	D	0.45	neutral	None	None	None	None	N
K/N	0.4165	ambiguous	0.5377	ambiguous	-0.057	Destabilizing	0.651	D	0.413	neutral	N	0.465805242	None	None	N
K/P	0.3528	ambiguous	0.418	ambiguous	0.219	Stabilizing	0.982	D	0.523	neutral	None	None	None	None	N
K/Q	0.1266	likely_benign	0.1603	benign	-0.176	Destabilizing	0.651	D	0.493	neutral	N	0.465298263	None	None	N
K/R	0.0744	likely_benign	0.0798	benign	-0.11	Destabilizing	0.001	N	0.177	neutral	N	0.43972723	None	None	N
K/S	0.3998	ambiguous	0.5127	ambiguous	-0.388	Destabilizing	0.712	D	0.459	neutral	None	None	None	None	N
K/T	0.2239	likely_benign	0.2984	benign	-0.277	Destabilizing	0.791	D	0.459	neutral	N	0.429624879	None	None	N
K/V	0.4412	ambiguous	0.5268	ambiguous	0.219	Stabilizing	0.946	D	0.572	neutral	None	None	None	None	N
K/W	0.7905	likely_pathogenic	0.8491	pathogenic	-0.429	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	N
K/Y	0.7264	likely_pathogenic	0.8043	pathogenic	-0.078	Destabilizing	0.982	D	0.595	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.