TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7834	23725;23726;23727	chr2:178720142;178720141;178720140	chr2:179584869;179584868;179584867
N2AB	7517	22774;22775;22776	chr2:178720142;178720141;178720140	chr2:179584869;179584868;179584867
N2A	6590	19993;19994;19995	chr2:178720142;178720141;178720140	chr2:179584869;179584868;179584867
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-63
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4825
• 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	0.036	D	0.302	0.136	0.220303561663	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85873E-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	0.1992	likely_benign	0.2108	benign	-0.72	Destabilizing	0.02	N	0.339	neutral	N	0.498658931	None	None	N
E/C	0.8691	likely_pathogenic	0.8879	pathogenic	-0.333	Destabilizing	0.685	D	0.357	neutral	None	None	None	None	N
E/D	0.0867	likely_benign	0.1007	benign	-0.674	Destabilizing	None	N	0.181	neutral	D	0.537177285	None	None	N
E/F	0.7096	likely_pathogenic	0.7448	pathogenic	-0.329	Destabilizing	0.148	N	0.361	neutral	None	None	None	None	N
E/G	0.2571	likely_benign	0.2606	benign	-0.995	Destabilizing	0.063	N	0.335	neutral	N	0.518537613	None	None	N
E/H	0.481	ambiguous	0.5137	ambiguous	-0.295	Destabilizing	None	N	0.185	neutral	None	None	None	None	N
E/I	0.3386	likely_benign	0.3742	ambiguous	0.002	Stabilizing	0.141	N	0.355	neutral	None	None	None	None	N
E/K	0.204	likely_benign	0.217	benign	-0.145	Destabilizing	0.036	N	0.302	neutral	D	0.534019549	None	None	N
E/L	0.4349	ambiguous	0.4458	ambiguous	0.002	Stabilizing	0.023	N	0.353	neutral	None	None	None	None	N
E/M	0.4856	ambiguous	0.5076	ambiguous	0.203	Stabilizing	0.253	N	0.319	neutral	None	None	None	None	N
E/N	0.2132	likely_benign	0.2469	benign	-0.612	Destabilizing	0.005	N	0.333	neutral	None	None	None	None	N
E/P	0.8286	likely_pathogenic	0.8106	pathogenic	-0.219	Destabilizing	0.024	N	0.362	neutral	None	None	None	None	N
E/Q	0.1867	likely_benign	0.193	benign	-0.528	Destabilizing	0.026	N	0.333	neutral	N	0.48609763	None	None	N
E/R	0.3459	ambiguous	0.3695	ambiguous	0.145	Stabilizing	0.148	N	0.329	neutral	None	None	None	None	N
E/S	0.2437	likely_benign	0.2656	benign	-0.797	Destabilizing	0.013	N	0.288	neutral	None	None	None	None	N
E/T	0.2788	likely_benign	0.291	benign	-0.572	Destabilizing	0.036	N	0.369	neutral	None	None	None	None	N
E/V	0.209	likely_benign	0.2276	benign	-0.219	Destabilizing	0.081	N	0.339	neutral	N	0.500913883	None	None	N
E/W	0.8907	likely_pathogenic	0.905	pathogenic	-0.079	Destabilizing	None	N	0.274	neutral	None	None	None	None	N
E/Y	0.5922	likely_pathogenic	0.6358	pathogenic	-0.08	Destabilizing	0.317	N	0.333	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.