TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19773	59542;59543;59544	chr2:178592802;178592801;178592800	chr2:179457529;179457528;179457527
N2AB	18132	54619;54620;54621	chr2:178592802;178592801;178592800	chr2:179457529;179457528;179457527
N2A	17205	51838;51839;51840	chr2:178592802;178592801;178592800	chr2:179457529;179457528;179457527
N2B	10708	32347;32348;32349	chr2:178592802;178592801;178592800	chr2:179457529;179457528;179457527
Novex-1	10833	32722;32723;32724	chr2:178592802;178592801;178592800	chr2:179457529;179457528;179457527
Novex-2	10900	32923;32924;32925	chr2:178592802;178592801;178592800	chr2:179457529;179457528;179457527
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: Fn3-31
• Domain position: 94
• Structural Position: 125
• Q(SASA): 0.7571
• Predicted PPI site: I

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/A	None	None	0.877	N	0.586	0.351	0.3571064206	gnomAD-4.0.0	6.84345E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99585E-07	0	0
E/G	rs371719028	-0.092	0.877	N	0.455	0.261	None	gnomAD-2.1.1	2.21626E-04	None	None	None	None	I	None	2.56241E-03	0	None	0	0	None	0	None	0	0	0
E/G	rs371719028	-0.092	0.877	N	0.455	0.261	None	gnomAD-3.1.2	7.23275E-04	None	None	None	None	I	None	2.58192E-03	1.96567E-04	0	0	0	None	0	0	0	0	0
E/G	rs371719028	-0.092	0.877	N	0.455	0.261	None	1000 genomes	5.99042E-04	None	None	None	None	I	None	2.3E-03	0	None	None	0	0	None	None	None	0	None
E/G	rs371719028	-0.092	0.877	N	0.455	0.261	None	gnomAD-4.0.0	1.19619E-04	None	None	None	None	I	None	2.46621E-03	5.00167E-05	None	0	0	None	0	0	0	0	8.00384E-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
E/A	0.1244	likely_benign	0.1191	benign	-0.082	Destabilizing	0.877	D	0.586	neutral	N	0.472477513	None	None	I
E/C	0.7241	likely_pathogenic	0.7044	pathogenic	-0.375	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
E/D	0.0687	likely_benign	0.0677	benign	-0.355	Destabilizing	0.009	N	0.162	neutral	N	0.461046651	None	None	I
E/F	0.5833	likely_pathogenic	0.5757	pathogenic	-0.106	Destabilizing	0.999	D	0.653	prob.neutral	None	None	None	None	I
E/G	0.1174	likely_benign	0.11	benign	-0.2	Destabilizing	0.877	D	0.455	neutral	N	0.479632412	None	None	I
E/H	0.3422	ambiguous	0.3259	benign	0.573	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	I
E/I	0.2791	likely_benign	0.2649	benign	0.175	Stabilizing	0.985	D	0.693	prob.delet.	None	None	None	None	I
E/K	0.1329	likely_benign	0.1254	benign	0.246	Stabilizing	0.877	D	0.556	neutral	N	0.465426848	None	None	I
E/L	0.28	likely_benign	0.2697	benign	0.175	Stabilizing	0.985	D	0.692	prob.delet.	None	None	None	None	I
E/M	0.3621	ambiguous	0.3482	ambiguous	-0.141	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
E/N	0.1388	likely_benign	0.1315	benign	0.008	Stabilizing	0.943	D	0.62	neutral	None	None	None	None	I
E/P	0.4048	ambiguous	0.4186	ambiguous	0.107	Stabilizing	0.985	D	0.649	prob.neutral	None	None	None	None	I
E/Q	0.1203	likely_benign	0.1159	benign	0.019	Stabilizing	0.981	D	0.623	neutral	N	0.500930404	None	None	I
E/R	0.2387	likely_benign	0.2301	benign	0.562	Stabilizing	0.985	D	0.676	prob.neutral	None	None	None	None	I
E/S	0.1314	likely_benign	0.1267	benign	-0.141	Destabilizing	0.904	D	0.551	neutral	None	None	None	None	I
E/T	0.1594	likely_benign	0.1555	benign	-0.038	Destabilizing	0.971	D	0.607	neutral	None	None	None	None	I
E/V	0.1707	likely_benign	0.1632	benign	0.107	Stabilizing	0.981	D	0.631	neutral	N	0.4763254	None	None	I
E/W	0.8232	likely_pathogenic	0.8126	pathogenic	-0.054	Destabilizing	0.999	D	0.687	prob.delet.	None	None	None	None	I
E/Y	0.4513	ambiguous	0.4373	ambiguous	0.113	Stabilizing	0.999	D	0.596	neutral	None	None	None	None	I

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.