TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21460	64603;64604;64605	chr2:178586523;178586522;178586521	chr2:179451250;179451249;179451248
N2AB	19819	59680;59681;59682	chr2:178586523;178586522;178586521	chr2:179451250;179451249;179451248
N2A	18892	56899;56900;56901	chr2:178586523;178586522;178586521	chr2:179451250;179451249;179451248
N2B	12395	37408;37409;37410	chr2:178586523;178586522;178586521	chr2:179451250;179451249;179451248
Novex-1	12520	37783;37784;37785	chr2:178586523;178586522;178586521	chr2:179451250;179451249;179451248
Novex-2	12587	37984;37985;37986	chr2:178586523;178586522;178586521	chr2:179451250;179451249;179451248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-43
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3525
• 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/K	None	None	0.997	N	0.776	0.387	0.466313656995	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86167E-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	0.2661	likely_benign	0.2316	benign	-0.73	Destabilizing	0.997	D	0.784	deleterious	N	0.479990276	None	None	N
E/C	0.8971	likely_pathogenic	0.8694	pathogenic	-0.381	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/D	0.322	likely_benign	0.2869	benign	-1.072	Destabilizing	0.997	D	0.676	prob.neutral	N	0.517508515	None	None	N
E/F	0.8198	likely_pathogenic	0.7751	pathogenic	-0.371	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
E/G	0.5375	ambiguous	0.4665	ambiguous	-1.052	Destabilizing	0.999	D	0.726	deleterious	N	0.487930828	None	None	N
E/H	0.6674	likely_pathogenic	0.5993	pathogenic	-0.578	Destabilizing	1.0	D	0.702	prob.delet.	None	None	None	None	N
E/I	0.2612	likely_benign	0.2263	benign	0.128	Stabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
E/K	0.3178	likely_benign	0.2544	benign	-0.522	Destabilizing	0.997	D	0.776	deleterious	N	0.482067789	None	None	N
E/L	0.3703	ambiguous	0.326	benign	0.128	Stabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
E/M	0.4545	ambiguous	0.4073	ambiguous	0.488	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/N	0.5406	ambiguous	0.4771	ambiguous	-0.895	Destabilizing	0.999	D	0.723	deleterious	None	None	None	None	N
E/P	0.776	likely_pathogenic	0.75	pathogenic	-0.136	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
E/Q	0.2189	likely_benign	0.1888	benign	-0.806	Destabilizing	0.999	D	0.671	prob.neutral	N	0.478355481	None	None	N
E/R	0.5065	ambiguous	0.4245	ambiguous	-0.244	Destabilizing	0.999	D	0.723	deleterious	None	None	None	None	N
E/S	0.4051	ambiguous	0.3519	ambiguous	-1.15	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
E/T	0.2223	likely_benign	0.1991	benign	-0.896	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
E/V	0.1561	likely_benign	0.1419	benign	-0.136	Destabilizing	0.999	D	0.79	deleterious	N	0.457500206	None	None	N
E/W	0.9528	likely_pathogenic	0.9353	pathogenic	-0.181	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/Y	0.774	likely_pathogenic	0.7107	pathogenic	-0.142	Destabilizing	1.0	D	0.869	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.