TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19823	59692;59693;59694	chr2:178592538;178592537;178592536	chr2:179457265;179457264;179457263
N2AB	18182	54769;54770;54771	chr2:178592538;178592537;178592536	chr2:179457265;179457264;179457263
N2A	17255	51988;51989;51990	chr2:178592538;178592537;178592536	chr2:179457265;179457264;179457263
N2B	10758	32497;32498;32499	chr2:178592538;178592537;178592536	chr2:179457265;179457264;179457263
Novex-1	10883	32872;32873;32874	chr2:178592538;178592537;178592536	chr2:179457265;179457264;179457263
Novex-2	10950	33073;33074;33075	chr2:178592538;178592537;178592536	chr2:179457265;179457264;179457263
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-119
• Domain position: 34
• Structural Position: 51
• Q(SASA): 0.3852
• 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/G	None	None	None	N	0.188	0.071	0.104622674875	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	2.28697E-05	None	0	0	None	0	0	0	0	0
E/K	None	None	0.117	N	0.286	0.176	0.190952846119	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	5.66316E-05	0	None	0	0	None	0	0	0	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	0.1466	likely_benign	0.1584	benign	-0.622	Destabilizing	0.027	N	0.271	neutral	N	0.456285832	None	None	N
E/C	0.8099	likely_pathogenic	0.8406	pathogenic	-0.216	Destabilizing	0.935	D	0.486	neutral	None	None	None	None	N
E/D	0.0966	likely_benign	0.1026	benign	-0.48	Destabilizing	0.027	N	0.275	neutral	N	0.371181503	None	None	N
E/F	0.7766	likely_pathogenic	0.8124	pathogenic	-0.314	Destabilizing	0.791	D	0.449	neutral	None	None	None	None	N
E/G	0.0763	likely_benign	0.0928	benign	-0.872	Destabilizing	None	N	0.188	neutral	N	0.431771389	None	None	N
E/H	0.5368	ambiguous	0.6117	pathogenic	-0.226	Destabilizing	0.555	D	0.304	neutral	None	None	None	None	N
E/I	0.5004	ambiguous	0.5535	ambiguous	0.021	Stabilizing	0.555	D	0.462	neutral	None	None	None	None	N
E/K	0.2347	likely_benign	0.2997	benign	0.036	Stabilizing	0.117	N	0.286	neutral	N	0.471561928	None	None	N
E/L	0.4297	ambiguous	0.4665	ambiguous	0.021	Stabilizing	0.38	N	0.429	neutral	None	None	None	None	N
E/M	0.4785	ambiguous	0.511	ambiguous	0.213	Stabilizing	0.935	D	0.429	neutral	None	None	None	None	N
E/N	0.1853	likely_benign	0.1941	benign	-0.373	Destabilizing	0.001	N	0.116	neutral	None	None	None	None	N
E/P	0.7688	likely_pathogenic	0.8551	pathogenic	-0.173	Destabilizing	0.555	D	0.339	neutral	None	None	None	None	N
E/Q	0.1678	likely_benign	0.1911	benign	-0.305	Destabilizing	0.211	N	0.333	neutral	N	0.465348032	None	None	N
E/R	0.317	likely_benign	0.3987	ambiguous	0.29	Stabilizing	0.262	N	0.304	neutral	None	None	None	None	N
E/S	0.2046	likely_benign	0.2293	benign	-0.565	Destabilizing	0.035	N	0.267	neutral	None	None	None	None	N
E/T	0.3243	likely_benign	0.3704	ambiguous	-0.359	Destabilizing	0.149	N	0.305	neutral	None	None	None	None	N
E/V	0.2976	likely_benign	0.3406	ambiguous	-0.173	Destabilizing	0.484	N	0.4	neutral	N	0.459403495	None	None	N
E/W	0.8859	likely_pathogenic	0.9277	pathogenic	-0.089	Destabilizing	0.935	D	0.533	neutral	None	None	None	None	N
E/Y	0.6079	likely_pathogenic	0.6722	pathogenic	-0.065	Destabilizing	0.791	D	0.428	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.