TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9367	28324;28325;28326	chr2:178711137;178711136;178711135	chr2:179575864;179575863;179575862
N2AB	9050	27373;27374;27375	chr2:178711137;178711136;178711135	chr2:179575864;179575863;179575862
N2A	8123	24592;24593;24594	chr2:178711137;178711136;178711135	chr2:179575864;179575863;179575862
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-79
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1217
• 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
L/F	rs748483786	-1.428	None	None	0.418	0.078	0.352693368174	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.12E-05	0
L/F	rs748483786	-1.428	None	None	0.418	0.078	0.352693368174	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
L/F	rs748483786	-1.428	None	None	0.418	0.078	0.352693368174	gnomAD-4.0.0	2.23083E-05	None	None	None	None	N	None	0	1.66689E-05	None	0	0	None	0	1.64474E-04	2.79708E-05	0	1.60092E-05

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
L/A	0.1885	likely_benign	0.2139	benign	-1.845	Destabilizing	0.149	N	0.729	prob.delet.	None	None	None	None	N
L/C	0.4263	ambiguous	0.4306	ambiguous	-1.357	Destabilizing	0.935	D	0.809	deleterious	None	None	None	None	N
L/D	0.38	ambiguous	0.4864	ambiguous	-0.645	Destabilizing	0.555	D	0.867	deleterious	None	None	None	None	N
L/E	0.2393	likely_benign	0.3157	benign	-0.545	Destabilizing	0.38	N	0.857	deleterious	None	None	None	None	N
L/F	0.0875	likely_benign	0.093	benign	-1.093	Destabilizing	None	N	0.418	neutral	None	None	None	None	N
L/G	0.4164	ambiguous	0.4964	ambiguous	-2.258	Highly Destabilizing	0.555	D	0.847	deleterious	None	None	None	None	N
L/H	0.095	likely_benign	0.1135	benign	-1.276	Destabilizing	None	N	0.577	neutral	None	None	None	None	N
L/I	0.1059	likely_benign	0.1125	benign	-0.74	Destabilizing	0.062	N	0.671	neutral	None	None	None	None	N
L/K	0.2525	likely_benign	0.3374	benign	-1.165	Destabilizing	0.38	N	0.849	deleterious	None	None	None	None	N
L/M	0.107	likely_benign	0.1044	benign	-0.747	Destabilizing	0.555	D	0.711	prob.delet.	None	None	None	None	N
L/N	0.2109	likely_benign	0.2671	benign	-1.161	Destabilizing	0.38	N	0.858	deleterious	None	None	None	None	N
L/P	0.6569	likely_pathogenic	0.8059	pathogenic	-1.08	Destabilizing	0.741	D	0.882	deleterious	None	None	None	None	N
L/Q	0.1054	likely_benign	0.1302	benign	-1.142	Destabilizing	0.38	N	0.866	deleterious	None	None	None	None	N
L/R	0.1787	likely_benign	0.2419	benign	-0.763	Destabilizing	0.317	N	0.857	deleterious	None	None	None	None	N
L/S	0.1592	likely_benign	0.1804	benign	-1.984	Destabilizing	0.149	N	0.84	deleterious	None	None	None	None	N
L/T	0.1689	likely_benign	0.1912	benign	-1.73	Destabilizing	0.262	N	0.806	deleterious	None	None	None	None	N
L/V	0.101	likely_benign	0.1064	benign	-1.08	Destabilizing	0.062	N	0.66	neutral	None	None	None	None	N
L/W	0.1446	likely_benign	0.1805	benign	-1.141	Destabilizing	0.824	D	0.853	deleterious	None	None	None	None	N
L/Y	0.1671	likely_benign	0.1884	benign	-0.93	Destabilizing	0.081	N	0.777	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.