TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20691	62296;62297;62298	chr2:178589654;178589653;178589652	chr2:179454381;179454380;179454379
N2AB	19050	57373;57374;57375	chr2:178589654;178589653;178589652	chr2:179454381;179454380;179454379
N2A	18123	54592;54593;54594	chr2:178589654;178589653;178589652	chr2:179454381;179454380;179454379
N2B	11626	35101;35102;35103	chr2:178589654;178589653;178589652	chr2:179454381;179454380;179454379
Novex-1	11751	35476;35477;35478	chr2:178589654;178589653;178589652	chr2:179454381;179454380;179454379
Novex-2	11818	35677;35678;35679	chr2:178589654;178589653;178589652	chr2:179454381;179454380;179454379
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-38
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6321
• 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
R/S	None	None	0.92	N	0.499	0.253	0.231873229951	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
R/A	0.7673	likely_pathogenic	0.775	pathogenic	0.123	Stabilizing	0.863	D	0.471	neutral	None	None	None	None	N
R/C	0.5431	ambiguous	0.5007	ambiguous	-0.081	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
R/D	0.9473	likely_pathogenic	0.9503	pathogenic	-0.164	Destabilizing	0.969	D	0.565	neutral	None	None	None	None	N
R/E	0.7591	likely_pathogenic	0.7756	pathogenic	-0.062	Destabilizing	0.863	D	0.534	neutral	None	None	None	None	N
R/F	0.8933	likely_pathogenic	0.8925	pathogenic	0.042	Stabilizing	0.997	D	0.607	neutral	None	None	None	None	N
R/G	0.7612	likely_pathogenic	0.7636	pathogenic	-0.112	Destabilizing	0.959	D	0.515	neutral	N	0.482520789	None	None	N
R/H	0.2943	likely_benign	0.3049	benign	-0.776	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	N
R/I	0.655	likely_pathogenic	0.6039	pathogenic	0.719	Stabilizing	0.997	D	0.601	neutral	None	None	None	None	N
R/K	0.1334	likely_benign	0.1419	benign	0.059	Stabilizing	0.021	N	0.216	neutral	N	0.397614035	None	None	N
R/L	0.5385	ambiguous	0.542	ambiguous	0.719	Stabilizing	0.969	D	0.515	neutral	None	None	None	None	N
R/M	0.6693	likely_pathogenic	0.6298	pathogenic	0.055	Stabilizing	0.996	D	0.582	neutral	N	0.509784748	None	None	N
R/N	0.8909	likely_pathogenic	0.8916	pathogenic	0.14	Stabilizing	0.969	D	0.534	neutral	None	None	None	None	N
R/P	0.6631	likely_pathogenic	0.6908	pathogenic	0.542	Stabilizing	0.997	D	0.587	neutral	None	None	None	None	N
R/Q	0.2509	likely_benign	0.2768	benign	0.153	Stabilizing	0.939	D	0.575	neutral	None	None	None	None	N
R/S	0.8663	likely_pathogenic	0.8683	pathogenic	-0.1	Destabilizing	0.92	D	0.499	neutral	N	0.508397881	None	None	N
R/T	0.7305	likely_pathogenic	0.7112	pathogenic	0.155	Stabilizing	0.959	D	0.505	neutral	N	0.489985479	None	None	N
R/V	0.7109	likely_pathogenic	0.6976	pathogenic	0.542	Stabilizing	0.991	D	0.587	neutral	None	None	None	None	N
R/W	0.6183	likely_pathogenic	0.6207	pathogenic	-0.042	Destabilizing	0.999	D	0.67	neutral	N	0.474838278	None	None	N
R/Y	0.7996	likely_pathogenic	0.8	pathogenic	0.365	Stabilizing	0.997	D	0.589	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.