TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14699	44320;44321;44322	chr2:178630863;178630862;178630861	chr2:179495590;179495589;179495588
N2AB	13058	39397;39398;39399	chr2:178630863;178630862;178630861	chr2:179495590;179495589;179495588
N2A	12131	36616;36617;36618	chr2:178630863;178630862;178630861	chr2:179495590;179495589;179495588
N2B	5634	17125;17126;17127	chr2:178630863;178630862;178630861	chr2:179495590;179495589;179495588
Novex-1	5759	17500;17501;17502	chr2:178630863;178630862;178630861	chr2:179495590;179495589;179495588
Novex-2	5826	17701;17702;17703	chr2:178630863;178630862;178630861	chr2:179495590;179495589;179495588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-98
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5299
• 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
S/C	rs1293270234	-0.246	1.0	D	0.677	0.465	0.340032825777	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	1.65893E-04
S/C	rs1293270234	-0.246	1.0	D	0.677	0.465	0.340032825777	gnomAD-4.0.0	4.77686E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58099E-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
S/A	0.4929	ambiguous	0.4711	ambiguous	-0.375	Destabilizing	0.994	D	0.343	neutral	D	0.609077008	None	None	N
S/C	0.7476	likely_pathogenic	0.7453	pathogenic	-0.364	Destabilizing	1.0	D	0.677	prob.neutral	D	0.613178089	None	None	N
S/D	0.8788	likely_pathogenic	0.8716	pathogenic	0.028	Stabilizing	0.998	D	0.608	neutral	None	None	None	None	N
S/E	0.9737	likely_pathogenic	0.9677	pathogenic	0.027	Stabilizing	0.998	D	0.591	neutral	None	None	None	None	N
S/F	0.9585	likely_pathogenic	0.9417	pathogenic	-0.531	Destabilizing	0.999	D	0.766	deleterious	D	0.611509329	None	None	N
S/G	0.5118	ambiguous	0.492	ambiguous	-0.625	Destabilizing	0.998	D	0.341	neutral	None	None	None	None	N
S/H	0.9624	likely_pathogenic	0.9566	pathogenic	-1.052	Destabilizing	1.0	D	0.671	prob.neutral	None	None	None	None	N
S/I	0.8913	likely_pathogenic	0.8612	pathogenic	0.173	Stabilizing	0.999	D	0.695	prob.delet.	None	None	None	None	N
S/K	0.9962	likely_pathogenic	0.9949	pathogenic	-0.618	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	N
S/L	0.6775	likely_pathogenic	0.6095	pathogenic	0.173	Stabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
S/M	0.8452	likely_pathogenic	0.8036	pathogenic	0.181	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
S/N	0.5984	likely_pathogenic	0.6148	pathogenic	-0.58	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	N
S/P	0.983	likely_pathogenic	0.973	pathogenic	0.026	Stabilizing	0.999	D	0.646	neutral	D	0.612432716	None	None	N
S/Q	0.9773	likely_pathogenic	0.9747	pathogenic	-0.641	Destabilizing	0.999	D	0.668	prob.neutral	None	None	None	None	N
S/R	0.993	likely_pathogenic	0.9906	pathogenic	-0.54	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
S/T	0.2155	likely_benign	0.1936	benign	-0.56	Destabilizing	0.997	D	0.409	neutral	D	0.568720859	None	None	N
S/V	0.8928	likely_pathogenic	0.8707	pathogenic	0.026	Stabilizing	0.999	D	0.728	deleterious	None	None	None	None	N
S/W	0.969	likely_pathogenic	0.9578	pathogenic	-0.599	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
S/Y	0.9303	likely_pathogenic	0.9063	pathogenic	-0.298	Destabilizing	0.999	D	0.768	deleterious	D	0.611509329	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.