TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31383	94372;94373;94374	chr2:178547479;178547478;178547477	chr2:179412206;179412205;179412204
N2AB	29742	89449;89450;89451	chr2:178547479;178547478;178547477	chr2:179412206;179412205;179412204
N2A	28815	86668;86669;86670	chr2:178547479;178547478;178547477	chr2:179412206;179412205;179412204
N2B	22318	67177;67178;67179	chr2:178547479;178547478;178547477	chr2:179412206;179412205;179412204
Novex-1	22443	67552;67553;67554	chr2:178547479;178547478;178547477	chr2:179412206;179412205;179412204
Novex-2	22510	67753;67754;67755	chr2:178547479;178547478;178547477	chr2:179412206;179412205;179412204
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-116
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0821
• 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/I	rs1336482759	None	0.016	D	0.336	0.224	0.417971555824	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1336482759	None	0.016	D	0.336	0.224	0.417971555824	gnomAD-4.0.0	6.57177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46964E-05	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	0.9161	likely_pathogenic	0.9006	pathogenic	-2.379	Highly Destabilizing	0.834	D	0.671	neutral	D	0.549023174	None	None	N
V/C	0.971	likely_pathogenic	0.973	pathogenic	-1.844	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9991	pathogenic	-3.44	Highly Destabilizing	0.973	D	0.905	deleterious	D	0.628787172	None	None	N
V/E	0.9961	likely_pathogenic	0.9964	pathogenic	-3.123	Highly Destabilizing	0.979	D	0.882	deleterious	None	None	None	None	N
V/F	0.9323	likely_pathogenic	0.9356	pathogenic	-1.338	Destabilizing	0.946	D	0.84	deleterious	D	0.567127429	None	None	N
V/G	0.9697	likely_pathogenic	0.9683	pathogenic	-2.978	Highly Destabilizing	0.973	D	0.897	deleterious	D	0.628787172	None	None	N
V/H	0.999	likely_pathogenic	0.9991	pathogenic	-2.914	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
V/I	0.0876	likely_benign	0.0874	benign	-0.631	Destabilizing	0.016	N	0.336	neutral	D	0.526925793	None	None	N
V/K	0.9968	likely_pathogenic	0.9974	pathogenic	-1.974	Destabilizing	0.979	D	0.885	deleterious	None	None	None	None	N
V/L	0.7424	likely_pathogenic	0.7428	pathogenic	-0.631	Destabilizing	0.263	N	0.625	neutral	N	0.518469296	None	None	N
V/M	0.8371	likely_pathogenic	0.8479	pathogenic	-0.917	Destabilizing	0.959	D	0.809	deleterious	None	None	None	None	N
V/N	0.9961	likely_pathogenic	0.9964	pathogenic	-2.656	Highly Destabilizing	0.993	D	0.915	deleterious	None	None	None	None	N
V/P	0.9966	likely_pathogenic	0.9971	pathogenic	-1.196	Destabilizing	0.993	D	0.903	deleterious	None	None	None	None	N
V/Q	0.9956	likely_pathogenic	0.9959	pathogenic	-2.3	Highly Destabilizing	0.993	D	0.913	deleterious	None	None	None	None	N
V/R	0.9934	likely_pathogenic	0.9942	pathogenic	-2.054	Highly Destabilizing	0.979	D	0.918	deleterious	None	None	None	None	N
V/S	0.9842	likely_pathogenic	0.9828	pathogenic	-3.14	Highly Destabilizing	0.979	D	0.886	deleterious	None	None	None	None	N
V/T	0.9618	likely_pathogenic	0.9532	pathogenic	-2.67	Highly Destabilizing	0.87	D	0.735	prob.delet.	None	None	None	None	N
V/W	0.999	likely_pathogenic	0.9992	pathogenic	-1.952	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
V/Y	0.9946	likely_pathogenic	0.9951	pathogenic	-1.629	Destabilizing	0.979	D	0.85	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.