TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14932	45019;45020;45021	chr2:178624486;178624485;178624484	chr2:179489213;179489212;179489211
N2AB	13291	40096;40097;40098	chr2:178624486;178624485;178624484	chr2:179489213;179489212;179489211
N2A	12364	37315;37316;37317	chr2:178624486;178624485;178624484	chr2:179489213;179489212;179489211
N2B	5867	17824;17825;17826	chr2:178624486;178624485;178624484	chr2:179489213;179489212;179489211
Novex-1	5992	18199;18200;18201	chr2:178624486;178624485;178624484	chr2:179489213;179489212;179489211
Novex-2	6059	18400;18401;18402	chr2:178624486;178624485;178624484	chr2:179489213;179489212;179489211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-100
• Domain position: 80
• Structural Position: 165
• Q(SASA): 0.5801
• 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/F	None	None	0.999	N	0.701	0.424	0.282575091529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1403	likely_benign	0.1286	benign	-0.553	Destabilizing	0.973	D	0.427	neutral	N	0.391243195	None	None	N
S/C	0.3965	ambiguous	0.2794	benign	-0.32	Destabilizing	1.0	D	0.699	prob.neutral	N	0.448933376	None	None	N
S/D	0.6906	likely_pathogenic	0.7407	pathogenic	-0.683	Destabilizing	0.996	D	0.615	neutral	None	None	None	None	N
S/E	0.6789	likely_pathogenic	0.7736	pathogenic	-0.76	Destabilizing	0.996	D	0.615	neutral	None	None	None	None	N
S/F	0.4252	ambiguous	0.4142	ambiguous	-1.115	Destabilizing	0.999	D	0.701	prob.neutral	N	0.437159539	None	None	N
S/G	0.2772	likely_benign	0.2146	benign	-0.694	Destabilizing	0.996	D	0.578	neutral	None	None	None	None	N
S/H	0.5964	likely_pathogenic	0.63	pathogenic	-1.316	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
S/I	0.3744	ambiguous	0.3836	ambiguous	-0.297	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
S/K	0.8554	likely_pathogenic	0.8909	pathogenic	-0.698	Destabilizing	0.996	D	0.612	neutral	None	None	None	None	N
S/L	0.3335	likely_benign	0.2881	benign	-0.297	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	N
S/M	0.4725	ambiguous	0.4254	ambiguous	0.243	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
S/N	0.3695	ambiguous	0.3488	ambiguous	-0.53	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
S/P	0.8955	likely_pathogenic	0.888	pathogenic	-0.354	Destabilizing	0.999	D	0.718	prob.delet.	N	0.494771351	None	None	N
S/Q	0.6757	likely_pathogenic	0.7502	pathogenic	-0.886	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
S/R	0.7641	likely_pathogenic	0.8175	pathogenic	-0.4	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
S/T	0.1141	likely_benign	0.1079	benign	-0.549	Destabilizing	0.543	D	0.351	neutral	N	0.34724639	None	None	N
S/V	0.3636	ambiguous	0.3447	ambiguous	-0.354	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
S/W	0.6748	likely_pathogenic	0.6857	pathogenic	-1.098	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
S/Y	0.4199	ambiguous	0.4126	ambiguous	-0.828	Destabilizing	0.999	D	0.699	prob.neutral	N	0.473629029	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.