TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33140	99643;99644;99645	chr2:178537789;178537788;178537787	chr2:179402516;179402515;179402514
N2AB	31499	94720;94721;94722	chr2:178537789;178537788;178537787	chr2:179402516;179402515;179402514
N2A	30572	91939;91940;91941	chr2:178537789;178537788;178537787	chr2:179402516;179402515;179402514
N2B	24075	72448;72449;72450	chr2:178537789;178537788;178537787	chr2:179402516;179402515;179402514
Novex-1	24200	72823;72824;72825	chr2:178537789;178537788;178537787	chr2:179402516;179402515;179402514
Novex-2	24267	73024;73025;73026	chr2:178537789;178537788;178537787	chr2:179402516;179402515;179402514
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-156
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.312
• 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	1.0	N	0.675	0.501	0.554156219314	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87315E-05	0	0	1.15934E-05	0
E/K	None	None	0.997	N	0.607	0.488	0.435152311215	gnomAD-4.0.0	6.84232E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15942E-05	0
E/Q	None	None	0.999	N	0.586	0.364	0.501247319706	gnomAD-4.0.0	6.84232E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99486E-07	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	0.3599	ambiguous	0.3478	ambiguous	-0.611	Destabilizing	0.995	D	0.644	neutral	N	0.486383105	None	None	N
E/C	0.9618	likely_pathogenic	0.9615	pathogenic	-0.536	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/D	0.5557	ambiguous	0.5937	pathogenic	-0.743	Destabilizing	0.965	D	0.46	neutral	N	0.518108734	None	None	N
E/F	0.9743	likely_pathogenic	0.9735	pathogenic	0.139	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/G	0.6361	likely_pathogenic	0.5973	pathogenic	-0.938	Destabilizing	1.0	D	0.675	prob.neutral	N	0.490393725	None	None	N
E/H	0.9159	likely_pathogenic	0.9105	pathogenic	0.294	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	N
E/I	0.6944	likely_pathogenic	0.6929	pathogenic	0.273	Stabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.5463	ambiguous	0.4796	ambiguous	-0.319	Destabilizing	0.997	D	0.607	neutral	N	0.472144371	None	None	N
E/L	0.7001	likely_pathogenic	0.7078	pathogenic	0.273	Stabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
E/M	0.7259	likely_pathogenic	0.7428	pathogenic	0.349	Stabilizing	0.998	D	0.671	neutral	None	None	None	None	N
E/N	0.7453	likely_pathogenic	0.7545	pathogenic	-0.949	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
E/P	0.6351	likely_pathogenic	0.6251	pathogenic	-0.002	Destabilizing	0.992	D	0.701	prob.neutral	None	None	None	None	N
E/Q	0.3436	ambiguous	0.3294	benign	-0.811	Destabilizing	0.999	D	0.586	neutral	N	0.505064866	None	None	N
E/R	0.7627	likely_pathogenic	0.7073	pathogenic	0.159	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
E/S	0.6738	likely_pathogenic	0.6777	pathogenic	-1.185	Destabilizing	0.997	D	0.624	neutral	None	None	None	None	N
E/T	0.6324	likely_pathogenic	0.64	pathogenic	-0.905	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
E/V	0.4799	ambiguous	0.4667	ambiguous	-0.002	Destabilizing	0.998	D	0.728	prob.delet.	N	0.494349227	None	None	N
E/W	0.9944	likely_pathogenic	0.9942	pathogenic	0.441	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/Y	0.9524	likely_pathogenic	0.9508	pathogenic	0.405	Stabilizing	1.0	D	0.699	prob.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.