TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16961	51106;51107;51108	chr2:178611248;178611247;178611246	chr2:179475975;179475974;179475973
N2AB	15320	46183;46184;46185	chr2:178611248;178611247;178611246	chr2:179475975;179475974;179475973
N2A	14393	43402;43403;43404	chr2:178611248;178611247;178611246	chr2:179475975;179475974;179475973
N2B	7896	23911;23912;23913	chr2:178611248;178611247;178611246	chr2:179475975;179475974;179475973
Novex-1	8021	24286;24287;24288	chr2:178611248;178611247;178611246	chr2:179475975;179475974;179475973
Novex-2	8088	24487;24488;24489	chr2:178611248;178611247;178611246	chr2:179475975;179475974;179475973
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-111
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1832
• 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/A	None	None	0.825	N	0.47	0.091	0.115124310173	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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	0.1034	likely_benign	0.1005	benign	-0.271	Destabilizing	0.825	D	0.47	neutral	N	0.436782143	None	None	N
T/C	0.4951	ambiguous	0.4987	ambiguous	-0.16	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/D	0.3811	ambiguous	0.3509	ambiguous	0.168	Stabilizing	0.991	D	0.727	prob.delet.	None	None	None	None	N
T/E	0.3358	likely_benign	0.3002	benign	0.117	Stabilizing	0.991	D	0.718	prob.delet.	None	None	None	None	N
T/F	0.3525	ambiguous	0.3391	benign	-0.686	Destabilizing	0.995	D	0.851	deleterious	None	None	None	None	N
T/G	0.2486	likely_benign	0.2435	benign	-0.421	Destabilizing	0.938	D	0.661	neutral	None	None	None	None	N
T/H	0.3146	likely_benign	0.2913	benign	-0.585	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
T/I	0.2793	likely_benign	0.2629	benign	0.012	Stabilizing	0.994	D	0.791	deleterious	N	0.44602335	None	None	N
T/K	0.2013	likely_benign	0.1883	benign	-0.28	Destabilizing	0.991	D	0.723	prob.delet.	None	None	None	None	N
T/L	0.161	likely_benign	0.1534	benign	0.012	Stabilizing	0.968	D	0.626	neutral	None	None	None	None	N
T/M	0.1176	likely_benign	0.1063	benign	-0.074	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/N	0.1122	likely_benign	0.105	benign	0.005	Stabilizing	0.988	D	0.656	neutral	N	0.436485595	None	None	N
T/P	0.2097	likely_benign	0.1646	benign	-0.054	Destabilizing	0.994	D	0.796	deleterious	N	0.419318272	None	None	N
T/Q	0.2432	likely_benign	0.2268	benign	-0.154	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
T/R	0.2	likely_benign	0.1847	benign	-0.024	Destabilizing	0.991	D	0.798	deleterious	None	None	None	None	N
T/S	0.1275	likely_benign	0.1254	benign	-0.191	Destabilizing	0.234	N	0.345	neutral	N	0.445116798	None	None	N
T/V	0.2302	likely_benign	0.2215	benign	-0.054	Destabilizing	0.968	D	0.509	neutral	None	None	None	None	N
T/W	0.6607	likely_pathogenic	0.659	pathogenic	-0.755	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
T/Y	0.3393	likely_benign	0.3337	benign	-0.459	Destabilizing	0.998	D	0.855	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.