TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25908	77947;77948;77949	chr2:178568410;178568409;178568408	chr2:179433137;179433136;179433135
N2AB	24267	73024;73025;73026	chr2:178568410;178568409;178568408	chr2:179433137;179433136;179433135
N2A	23340	70243;70244;70245	chr2:178568410;178568409;178568408	chr2:179433137;179433136;179433135
N2B	16843	50752;50753;50754	chr2:178568410;178568409;178568408	chr2:179433137;179433136;179433135
Novex-1	16968	51127;51128;51129	chr2:178568410;178568409;178568408	chr2:179433137;179433136;179433135
Novex-2	17035	51328;51329;51330	chr2:178568410;178568409;178568408	chr2:179433137;179433136;179433135
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-76
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.0493
• 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
I/N	None	None	0.879	N	0.83	0.503	0.840766441124	gnomAD-4.0.0	9.5822E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25946E-05	0	0
I/V	None	None	0.001	N	0.195	0.091	0.378498632473	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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
I/A	0.6024	likely_pathogenic	0.6479	pathogenic	-3.026	Highly Destabilizing	0.218	N	0.699	prob.neutral	None	None	None	None	N
I/C	0.7447	likely_pathogenic	0.718	pathogenic	-2.652	Highly Destabilizing	0.973	D	0.785	deleterious	None	None	None	None	N
I/D	0.9967	likely_pathogenic	0.9979	pathogenic	-3.268	Highly Destabilizing	0.906	D	0.833	deleterious	None	None	None	None	N
I/E	0.9921	likely_pathogenic	0.9949	pathogenic	-2.951	Highly Destabilizing	0.906	D	0.819	deleterious	None	None	None	None	N
I/F	0.4846	ambiguous	0.5057	ambiguous	-1.935	Destabilizing	0.782	D	0.708	prob.delet.	N	0.478956563	None	None	N
I/G	0.9582	likely_pathogenic	0.9659	pathogenic	-3.625	Highly Destabilizing	0.906	D	0.797	deleterious	None	None	None	None	N
I/H	0.9881	likely_pathogenic	0.9921	pathogenic	-3.202	Highly Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	N
I/K	0.9861	likely_pathogenic	0.9907	pathogenic	-2.191	Highly Destabilizing	0.826	D	0.803	deleterious	None	None	None	None	N
I/L	0.1366	likely_benign	0.1326	benign	-1.217	Destabilizing	0.031	N	0.416	neutral	N	0.445866555	None	None	N
I/M	0.1192	likely_benign	0.1138	benign	-1.624	Destabilizing	0.038	N	0.454	neutral	N	0.512038406	None	None	N
I/N	0.9607	likely_pathogenic	0.9724	pathogenic	-2.836	Highly Destabilizing	0.879	D	0.83	deleterious	N	0.511899843	None	None	N
I/P	0.9964	likely_pathogenic	0.9973	pathogenic	-1.812	Destabilizing	0.967	D	0.835	deleterious	None	None	None	None	N
I/Q	0.9795	likely_pathogenic	0.9858	pathogenic	-2.504	Highly Destabilizing	0.906	D	0.829	deleterious	None	None	None	None	N
I/R	0.9774	likely_pathogenic	0.984	pathogenic	-2.216	Highly Destabilizing	0.906	D	0.837	deleterious	None	None	None	None	N
I/S	0.866	likely_pathogenic	0.8981	pathogenic	-3.504	Highly Destabilizing	0.782	D	0.781	deleterious	N	0.500290048	None	None	N
I/T	0.7539	likely_pathogenic	0.8168	pathogenic	-3.014	Highly Destabilizing	0.338	N	0.779	deleterious	N	0.493453193	None	None	N
I/V	0.0642	likely_benign	0.0621	benign	-1.812	Destabilizing	0.001	N	0.195	neutral	N	0.371616726	None	None	N
I/W	0.9903	likely_pathogenic	0.9926	pathogenic	-2.157	Highly Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
I/Y	0.9546	likely_pathogenic	0.9619	pathogenic	-2.03	Highly Destabilizing	0.906	D	0.826	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.