TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17912	53959;53960;53961	chr2:178605561;178605560;178605559	chr2:179470288;179470287;179470286
N2AB	16271	49036;49037;49038	chr2:178605561;178605560;178605559	chr2:179470288;179470287;179470286
N2A	15344	46255;46256;46257	chr2:178605561;178605560;178605559	chr2:179470288;179470287;179470286
N2B	8847	26764;26765;26766	chr2:178605561;178605560;178605559	chr2:179470288;179470287;179470286
Novex-1	8972	27139;27140;27141	chr2:178605561;178605560;178605559	chr2:179470288;179470287;179470286
Novex-2	9039	27340;27341;27342	chr2:178605561;178605560;178605559	chr2:179470288;179470287;179470286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-18
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1731
• 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
V/F	None	None	0.032	D	0.382	0.243	0.389126455913	gnomAD-4.0.0	4.98543E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.62515E-05	0	3.71477E-06	0	0
V/L	None	None	0.489	N	0.527	0.132	0.273938319068	gnomAD-4.0.0	7.12155E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.28645E-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
V/A	0.2121	likely_benign	0.2583	benign	-1.59	Destabilizing	0.489	N	0.532	neutral	N	0.448850932	None	None	N
V/C	0.6074	likely_pathogenic	0.6219	pathogenic	-1.046	Destabilizing	0.019	N	0.402	neutral	None	None	None	None	N
V/D	0.8408	likely_pathogenic	0.8839	pathogenic	-1.705	Destabilizing	0.99	D	0.742	deleterious	N	0.492777949	None	None	N
V/E	0.7068	likely_pathogenic	0.759	pathogenic	-1.574	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
V/F	0.4042	ambiguous	0.4971	ambiguous	-1.006	Destabilizing	0.032	N	0.382	neutral	D	0.522079254	None	None	N
V/G	0.4328	ambiguous	0.5092	ambiguous	-2.036	Highly Destabilizing	0.97	D	0.697	prob.neutral	N	0.485398116	None	None	N
V/H	0.8769	likely_pathogenic	0.9109	pathogenic	-1.661	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
V/I	0.0936	likely_benign	0.0977	benign	-0.407	Destabilizing	0.489	N	0.555	neutral	N	0.493641859	None	None	N
V/K	0.8552	likely_pathogenic	0.8882	pathogenic	-1.374	Destabilizing	0.978	D	0.702	prob.neutral	None	None	None	None	N
V/L	0.3107	likely_benign	0.3969	ambiguous	-0.407	Destabilizing	0.489	N	0.527	neutral	N	0.478653764	None	None	N
V/M	0.3046	likely_benign	0.3688	ambiguous	-0.332	Destabilizing	0.978	D	0.579	neutral	None	None	None	None	N
V/N	0.7258	likely_pathogenic	0.774	pathogenic	-1.469	Destabilizing	0.993	D	0.746	deleterious	None	None	None	None	N
V/P	0.896	likely_pathogenic	0.9072	pathogenic	-0.769	Destabilizing	0.993	D	0.718	prob.delet.	None	None	None	None	N
V/Q	0.7357	likely_pathogenic	0.7818	pathogenic	-1.434	Destabilizing	0.993	D	0.713	prob.delet.	None	None	None	None	N
V/R	0.8218	likely_pathogenic	0.8596	pathogenic	-1.07	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
V/S	0.464	ambiguous	0.5271	ambiguous	-2.053	Highly Destabilizing	0.956	D	0.672	neutral	None	None	None	None	N
V/T	0.3564	ambiguous	0.4116	ambiguous	-1.786	Destabilizing	0.86	D	0.539	neutral	None	None	None	None	N
V/W	0.946	likely_pathogenic	0.9656	pathogenic	-1.409	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/Y	0.8046	likely_pathogenic	0.8496	pathogenic	-1.004	Destabilizing	0.915	D	0.676	prob.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.