TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6204	18835;18836;18837	chr2:178729546;178729545;178729544	chr2:179594273;179594272;179594271
N2AB	5887	17884;17885;17886	chr2:178729546;178729545;178729544	chr2:179594273;179594272;179594271
N2A	4960	15103;15104;15105	chr2:178729546;178729545;178729544	chr2:179594273;179594272;179594271
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-46
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5574
• 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
E/D	None	None	0.012	N	0.1	0.211	0.297718772494	gnomAD-4.0.0	6.8457E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99873E-07	0	0
E/G	None	None	0.801	N	0.36	0.234	0.502815669512	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs949942051	None	0.454	N	0.252	0.262	0.346315397577	gnomAD-4.0.0	1.36917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79979E-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
E/A	0.1147	likely_benign	0.1297	benign	-0.758	Destabilizing	0.454	N	0.289	neutral	N	0.513182917	None	None	N
E/C	0.7478	likely_pathogenic	0.7725	pathogenic	-0.398	Destabilizing	0.998	D	0.359	neutral	None	None	None	None	N
E/D	0.1688	likely_benign	0.1933	benign	-0.678	Destabilizing	0.012	N	0.1	neutral	N	0.521053039	None	None	N
E/F	0.6444	likely_pathogenic	0.676	pathogenic	-0.055	Destabilizing	0.974	D	0.371	neutral	None	None	None	None	N
E/G	0.1226	likely_benign	0.1378	benign	-1.088	Destabilizing	0.801	D	0.36	neutral	N	0.503448713	None	None	N
E/H	0.3687	ambiguous	0.3907	ambiguous	-0.068	Destabilizing	0.974	D	0.32	neutral	None	None	None	None	N
E/I	0.2904	likely_benign	0.3332	benign	0.134	Stabilizing	0.949	D	0.395	neutral	None	None	None	None	N
E/K	0.0946	likely_benign	0.0968	benign	-0.192	Destabilizing	0.454	N	0.252	neutral	N	0.475701965	None	None	N
E/L	0.278	likely_benign	0.2997	benign	0.134	Stabilizing	0.728	D	0.421	neutral	None	None	None	None	N
E/M	0.3303	likely_benign	0.3597	ambiguous	0.367	Stabilizing	0.998	D	0.345	neutral	None	None	None	None	N
E/N	0.2198	likely_benign	0.2551	benign	-0.775	Destabilizing	0.842	D	0.262	neutral	None	None	None	None	N
E/P	0.2443	likely_benign	0.2565	benign	-0.142	Destabilizing	0.016	N	0.18	neutral	None	None	None	None	N
E/Q	0.0985	likely_benign	0.0991	benign	-0.647	Destabilizing	0.136	N	0.087	neutral	N	0.510489329	None	None	N
E/R	0.1807	likely_benign	0.1771	benign	0.165	Stabilizing	0.842	D	0.299	neutral	None	None	None	None	N
E/S	0.1689	likely_benign	0.1923	benign	-1.023	Destabilizing	0.525	D	0.248	neutral	None	None	None	None	N
E/T	0.1506	likely_benign	0.1819	benign	-0.739	Destabilizing	0.067	N	0.225	neutral	None	None	None	None	N
E/V	0.1658	likely_benign	0.1871	benign	-0.142	Destabilizing	0.669	D	0.409	neutral	N	0.518474094	None	None	N
E/W	0.8459	likely_pathogenic	0.8657	pathogenic	0.289	Stabilizing	0.998	D	0.411	neutral	None	None	None	None	N
E/Y	0.5	ambiguous	0.5344	ambiguous	0.23	Stabilizing	0.991	D	0.37	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.