TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21341	64246;64247;64248	chr2:178587190;178587189;178587188	chr2:179451917;179451916;179451915
N2AB	19700	59323;59324;59325	chr2:178587190;178587189;178587188	chr2:179451917;179451916;179451915
N2A	18773	56542;56543;56544	chr2:178587190;178587189;178587188	chr2:179451917;179451916;179451915
N2B	12276	37051;37052;37053	chr2:178587190;178587189;178587188	chr2:179451917;179451916;179451915
Novex-1	12401	37426;37427;37428	chr2:178587190;178587189;178587188	chr2:179451917;179451916;179451915
Novex-2	12468	37627;37628;37629	chr2:178587190;178587189;178587188	chr2:179451917;179451916;179451915
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: Fn3-42
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.1532
• 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/I	None	None	0.977	N	0.771	0.289	0.326074293725	gnomAD-4.0.0	1.59221E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
T/S	None	None	0.98	N	0.727	0.255	0.245101548738	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-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	0.1103	likely_benign	0.1212	benign	-1.846	Destabilizing	0.91	D	0.713	prob.delet.	N	0.452755242	None	None	N
T/C	0.2842	likely_benign	0.3114	benign	-1.59	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/D	0.8192	likely_pathogenic	0.8442	pathogenic	-2.347	Highly Destabilizing	0.996	D	0.77	deleterious	None	None	None	None	N
T/E	0.6651	likely_pathogenic	0.6689	pathogenic	-2.137	Highly Destabilizing	0.991	D	0.768	deleterious	None	None	None	None	N
T/F	0.3591	ambiguous	0.4067	ambiguous	-1.306	Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
T/G	0.3659	ambiguous	0.3988	ambiguous	-2.199	Highly Destabilizing	0.985	D	0.763	deleterious	None	None	None	None	N
T/H	0.4519	ambiguous	0.4824	ambiguous	-2.002	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/I	0.174	likely_benign	0.1748	benign	-0.904	Destabilizing	0.977	D	0.771	deleterious	N	0.424955352	None	None	N
T/K	0.4986	ambiguous	0.5039	ambiguous	-1.154	Destabilizing	0.942	D	0.768	deleterious	None	None	None	None	N
T/L	0.0935	likely_benign	0.1011	benign	-0.904	Destabilizing	0.871	D	0.725	prob.delet.	None	None	None	None	N
T/M	0.0754	likely_benign	0.0805	benign	-1.138	Destabilizing	0.746	D	0.569	neutral	None	None	None	None	N
T/N	0.2524	likely_benign	0.2914	benign	-1.765	Destabilizing	0.994	D	0.771	deleterious	N	0.46693824	None	None	N
T/P	0.8919	likely_pathogenic	0.9268	pathogenic	-1.194	Destabilizing	0.998	D	0.787	deleterious	N	0.474700147	None	None	N
T/Q	0.4048	ambiguous	0.4096	ambiguous	-1.562	Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	N
T/R	0.3866	ambiguous	0.4021	ambiguous	-1.203	Destabilizing	0.191	N	0.587	neutral	None	None	None	None	N
T/S	0.1428	likely_benign	0.1629	benign	-1.958	Destabilizing	0.98	D	0.727	prob.delet.	N	0.43940473	None	None	N
T/V	0.1326	likely_benign	0.1351	benign	-1.194	Destabilizing	0.942	D	0.727	prob.delet.	None	None	None	None	N
T/W	0.7284	likely_pathogenic	0.7536	pathogenic	-1.441	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/Y	0.4253	ambiguous	0.454	ambiguous	-1.138	Destabilizing	0.999	D	0.808	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.