TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23590	70993;70994;70995	chr2:178575364;178575363;178575362	chr2:179440091;179440090;179440089
N2AB	21949	66070;66071;66072	chr2:178575364;178575363;178575362	chr2:179440091;179440090;179440089
N2A	21022	63289;63290;63291	chr2:178575364;178575363;178575362	chr2:179440091;179440090;179440089
N2B	14525	43798;43799;43800	chr2:178575364;178575363;178575362	chr2:179440091;179440090;179440089
Novex-1	14650	44173;44174;44175	chr2:178575364;178575363;178575362	chr2:179440091;179440090;179440089
Novex-2	14717	44374;44375;44376	chr2:178575364;178575363;178575362	chr2:179440091;179440090;179440089
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-59
• Domain position: 59
• Structural Position: 91
• Q(SASA): 0.1223
• 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
C/S	None	None	0.784	N	0.603	0.424	0.574465425021	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02444E-05

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
C/A	0.3431	ambiguous	0.3406	ambiguous	-1.532	Destabilizing	0.495	N	0.369	neutral	None	None	None	None	N
C/D	0.8514	likely_pathogenic	0.8407	pathogenic	0.195	Stabilizing	0.981	D	0.702	prob.neutral	None	None	None	None	N
C/E	0.8851	likely_pathogenic	0.8748	pathogenic	0.315	Stabilizing	0.944	D	0.709	prob.delet.	None	None	None	None	N
C/F	0.1795	likely_benign	0.1819	benign	-0.926	Destabilizing	0.002	N	0.467	neutral	N	0.445058479	None	None	N
C/G	0.2343	likely_benign	0.2217	benign	-1.842	Destabilizing	0.784	D	0.647	neutral	N	0.501818625	None	None	N
C/H	0.5328	ambiguous	0.5218	ambiguous	-1.672	Destabilizing	0.893	D	0.67	neutral	None	None	None	None	N
C/I	0.5137	ambiguous	0.4892	ambiguous	-0.739	Destabilizing	0.704	D	0.598	neutral	None	None	None	None	N
C/K	0.9015	likely_pathogenic	0.8946	pathogenic	-0.496	Destabilizing	0.828	D	0.711	prob.delet.	None	None	None	None	N
C/L	0.4531	ambiguous	0.4401	ambiguous	-0.739	Destabilizing	0.329	N	0.581	neutral	None	None	None	None	N
C/M	0.533	ambiguous	0.5371	ambiguous	0.067	Stabilizing	0.981	D	0.606	neutral	None	None	None	None	N
C/N	0.6163	likely_pathogenic	0.5963	pathogenic	-0.637	Destabilizing	0.944	D	0.675	prob.neutral	None	None	None	None	N
C/P	0.993	likely_pathogenic	0.9919	pathogenic	-0.977	Destabilizing	0.981	D	0.677	prob.neutral	None	None	None	None	N
C/Q	0.7697	likely_pathogenic	0.7572	pathogenic	-0.446	Destabilizing	0.981	D	0.677	prob.neutral	None	None	None	None	N
C/R	0.7163	likely_pathogenic	0.6936	pathogenic	-0.464	Destabilizing	0.927	D	0.68	prob.neutral	N	0.4721028	None	None	N
C/S	0.3551	ambiguous	0.3467	ambiguous	-1.211	Destabilizing	0.784	D	0.603	neutral	N	0.516729363	None	None	N
C/T	0.4291	ambiguous	0.4234	ambiguous	-0.889	Destabilizing	0.828	D	0.608	neutral	None	None	None	None	N
C/V	0.4086	ambiguous	0.3915	ambiguous	-0.977	Destabilizing	0.495	N	0.54	neutral	None	None	None	None	N
C/W	0.5653	likely_pathogenic	0.5693	pathogenic	-0.906	Destabilizing	0.927	D	0.611	neutral	N	0.468481949	None	None	N
C/Y	0.2142	likely_benign	0.2154	benign	-0.865	Destabilizing	0.001	N	0.449	neutral	N	0.413367348	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.