TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8229	24910;24911;24912	chr2:178718421;178718420;178718419	chr2:179583148;179583147;179583146
N2AB	7912	23959;23960;23961	chr2:178718421;178718420;178718419	chr2:179583148;179583147;179583146
N2A	6985	21178;21179;21180	chr2:178718421;178718420;178718419	chr2:179583148;179583147;179583146
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-67
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3234
• 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	rs761867872	-1.062	0.99	N	0.579	0.325	0.394230963961	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs761867872	-1.062	0.99	N	0.579	0.325	0.394230963961	gnomAD-4.0.0	6.84215E-07	None	None	None	None	N	None	2.98793E-05	0	None	0	0	None	0	0	0	0	0
E/K	None	None	0.4	N	0.335	0.277	0.300784259202	gnomAD-4.0.0	1.59132E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88253E-05	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	0.6151	likely_pathogenic	0.6927	pathogenic	-0.981	Destabilizing	0.98	D	0.607	neutral	N	0.516812412	None	None	N
E/C	0.9787	likely_pathogenic	0.983	pathogenic	-0.51	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.6541	likely_pathogenic	0.6906	pathogenic	-1.172	Destabilizing	0.99	D	0.579	neutral	N	0.509686068	None	None	N
E/F	0.969	likely_pathogenic	0.9765	pathogenic	-0.488	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
E/G	0.7167	likely_pathogenic	0.7766	pathogenic	-1.366	Destabilizing	0.135	N	0.489	neutral	N	0.518079859	None	None	N
E/H	0.8063	likely_pathogenic	0.8668	pathogenic	-0.818	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/I	0.831	likely_pathogenic	0.8729	pathogenic	0.079	Stabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
E/K	0.5684	likely_pathogenic	0.7132	pathogenic	-0.629	Destabilizing	0.4	N	0.335	neutral	N	0.517839376	None	None	N
E/L	0.8607	likely_pathogenic	0.891	pathogenic	0.079	Stabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
E/M	0.8605	likely_pathogenic	0.8838	pathogenic	0.593	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/N	0.7686	likely_pathogenic	0.822	pathogenic	-1.099	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
E/P	0.9973	likely_pathogenic	0.9978	pathogenic	-0.254	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.2966	likely_benign	0.372	ambiguous	-0.95	Destabilizing	0.98	D	0.595	neutral	N	0.4841623	None	None	N
E/R	0.6862	likely_pathogenic	0.8001	pathogenic	-0.467	Destabilizing	0.971	D	0.581	neutral	None	None	None	None	N
E/S	0.6528	likely_pathogenic	0.7129	pathogenic	-1.493	Destabilizing	0.985	D	0.571	neutral	None	None	None	None	N
E/T	0.6391	likely_pathogenic	0.6981	pathogenic	-1.156	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
E/V	0.6046	likely_pathogenic	0.6746	pathogenic	-0.254	Destabilizing	0.997	D	0.679	prob.neutral	D	0.525573424	None	None	N
E/W	0.9905	likely_pathogenic	0.9918	pathogenic	-0.258	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/Y	0.9378	likely_pathogenic	0.9556	pathogenic	-0.216	Destabilizing	0.999	D	0.719	prob.delet.	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.