TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32610	98053;98054;98055	chr2:178540338;178540337;178540336	chr2:179405065;179405064;179405063
N2AB	30969	93130;93131;93132	chr2:178540338;178540337;178540336	chr2:179405065;179405064;179405063
N2A	30042	90349;90350;90351	chr2:178540338;178540337;178540336	chr2:179405065;179405064;179405063
N2B	23545	70858;70859;70860	chr2:178540338;178540337;178540336	chr2:179405065;179405064;179405063
Novex-1	23670	71233;71234;71235	chr2:178540338;178540337;178540336	chr2:179405065;179405064;179405063
Novex-2	23737	71434;71435;71436	chr2:178540338;178540337;178540336	chr2:179405065;179405064;179405063
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: Fn3-126
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3624
• 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	0.999	N	0.545	0.355	0.259272394797	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8599E-06	0	0
T/I	None	None	1.0	N	0.799	0.424	0.52714902651	gnomAD-4.0.0	1.59201E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-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
T/A	0.2373	likely_benign	0.228	benign	-0.575	Destabilizing	0.999	D	0.545	neutral	N	0.475714105	None	None	N
T/C	0.6688	likely_pathogenic	0.6477	pathogenic	-0.295	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
T/D	0.9084	likely_pathogenic	0.8813	pathogenic	-0.022	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/E	0.8022	likely_pathogenic	0.7633	pathogenic	-0.078	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/F	0.6465	likely_pathogenic	0.6115	pathogenic	-0.891	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
T/G	0.701	likely_pathogenic	0.6729	pathogenic	-0.756	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/H	0.7632	likely_pathogenic	0.7243	pathogenic	-1.046	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
T/I	0.2951	likely_benign	0.281	benign	-0.203	Destabilizing	1.0	D	0.799	deleterious	N	0.479980066	None	None	N
T/K	0.5502	ambiguous	0.5178	ambiguous	-0.516	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/L	0.2021	likely_benign	0.1915	benign	-0.203	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
T/M	0.1358	likely_benign	0.1379	benign	0.128	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
T/N	0.5537	ambiguous	0.4981	ambiguous	-0.297	Destabilizing	1.0	D	0.694	prob.neutral	N	0.496464933	None	None	N
T/P	0.8132	likely_pathogenic	0.787	pathogenic	-0.297	Destabilizing	1.0	D	0.807	deleterious	N	0.506442113	None	None	N
T/Q	0.6408	likely_pathogenic	0.6058	pathogenic	-0.567	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/R	0.5227	ambiguous	0.4874	ambiguous	-0.192	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/S	0.3787	ambiguous	0.3534	ambiguous	-0.558	Destabilizing	0.999	D	0.535	neutral	N	0.498276888	None	None	N
T/V	0.1952	likely_benign	0.191	benign	-0.297	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
T/W	0.8876	likely_pathogenic	0.8761	pathogenic	-0.824	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/Y	0.741	likely_pathogenic	0.705	pathogenic	-0.58	Destabilizing	1.0	D	0.791	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.