TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14875	44848;44849;44850	chr2:178624657;178624656;178624655	chr2:179489384;179489383;179489382
N2AB	13234	39925;39926;39927	chr2:178624657;178624656;178624655	chr2:179489384;179489383;179489382
N2A	12307	37144;37145;37146	chr2:178624657;178624656;178624655	chr2:179489384;179489383;179489382
N2B	5810	17653;17654;17655	chr2:178624657;178624656;178624655	chr2:179489384;179489383;179489382
Novex-1	5935	18028;18029;18030	chr2:178624657;178624656;178624655	chr2:179489384;179489383;179489382
Novex-2	6002	18229;18230;18231	chr2:178624657;178624656;178624655	chr2:179489384;179489383;179489382
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: Ig-100
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2656
• 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	0.999	D	0.461	0.274	0.28722502521	gnomAD-4.0.0	1.59385E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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	0.3768	ambiguous	0.3424	ambiguous	-0.902	Destabilizing	0.999	D	0.647	neutral	D	0.544071917	None	None	N
E/C	0.9631	likely_pathogenic	0.9624	pathogenic	-0.673	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.6311	likely_pathogenic	0.5787	pathogenic	-1.467	Destabilizing	0.999	D	0.461	neutral	D	0.587051611	None	None	N
E/F	0.938	likely_pathogenic	0.9315	pathogenic	-0.85	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.6741	likely_pathogenic	0.6222	pathogenic	-1.252	Destabilizing	1.0	D	0.733	prob.delet.	D	0.621298269	None	None	N
E/H	0.8349	likely_pathogenic	0.8067	pathogenic	-1.211	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.6028	likely_pathogenic	0.621	pathogenic	0.053	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/K	0.476	ambiguous	0.4153	ambiguous	-1.079	Destabilizing	0.999	D	0.537	neutral	N	0.496638531	None	None	N
E/L	0.7582	likely_pathogenic	0.7444	pathogenic	0.053	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/M	0.7315	likely_pathogenic	0.7126	pathogenic	0.575	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.7899	likely_pathogenic	0.7455	pathogenic	-1.318	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/P	0.9884	likely_pathogenic	0.9844	pathogenic	-0.244	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Q	0.3116	likely_benign	0.2744	benign	-1.181	Destabilizing	1.0	D	0.592	neutral	N	0.502125148	None	None	N
E/R	0.6228	likely_pathogenic	0.5814	pathogenic	-0.967	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/S	0.5767	likely_pathogenic	0.5337	ambiguous	-1.742	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
E/T	0.5031	ambiguous	0.4932	ambiguous	-1.447	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/V	0.3921	ambiguous	0.3966	ambiguous	-0.244	Destabilizing	1.0	D	0.779	deleterious	D	0.559519851	None	None	N
E/W	0.9838	likely_pathogenic	0.9822	pathogenic	-0.872	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.922	likely_pathogenic	0.9127	pathogenic	-0.668	Destabilizing	1.0	D	0.788	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.