TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17620	53083;53084;53085	chr2:178607929;178607928;178607927	chr2:179472656;179472655;179472654
N2AB	15979	48160;48161;48162	chr2:178607929;178607928;178607927	chr2:179472656;179472655;179472654
N2A	15052	45379;45380;45381	chr2:178607929;178607928;178607927	chr2:179472656;179472655;179472654
N2B	8555	25888;25889;25890	chr2:178607929;178607928;178607927	chr2:179472656;179472655;179472654
Novex-1	8680	26263;26264;26265	chr2:178607929;178607928;178607927	chr2:179472656;179472655;179472654
Novex-2	8747	26464;26465;26466	chr2:178607929;178607928;178607927	chr2:179472656;179472655;179472654
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-16
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1585
• 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
T/I	None	None	0.991	N	0.665	0.363	0.572964795716	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
T/R	rs1559743128	None	0.982	D	0.649	0.338	0.71323274049	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
T/A	0.3587	ambiguous	0.3485	ambiguous	-1.023	Destabilizing	0.76	D	0.484	neutral	N	0.477579116	None	None	N
T/C	0.7741	likely_pathogenic	0.7533	pathogenic	-0.575	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
T/D	0.8332	likely_pathogenic	0.8296	pathogenic	-0.8	Destabilizing	0.91	D	0.563	neutral	None	None	None	None	N
T/E	0.8665	likely_pathogenic	0.8428	pathogenic	-0.644	Destabilizing	0.953	D	0.571	neutral	None	None	None	None	N
T/F	0.8894	likely_pathogenic	0.8613	pathogenic	-0.714	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
T/G	0.5838	likely_pathogenic	0.594	pathogenic	-1.421	Destabilizing	0.91	D	0.529	neutral	None	None	None	None	N
T/H	0.6993	likely_pathogenic	0.6654	pathogenic	-1.528	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	N
T/I	0.7609	likely_pathogenic	0.7129	pathogenic	0.003	Stabilizing	0.991	D	0.665	neutral	N	0.518270945	None	None	N
T/K	0.7993	likely_pathogenic	0.7735	pathogenic	-0.548	Destabilizing	0.939	D	0.58	neutral	N	0.510920898	None	None	N
T/L	0.4984	ambiguous	0.4492	ambiguous	0.003	Stabilizing	0.976	D	0.565	neutral	None	None	None	None	N
T/M	0.3699	ambiguous	0.3121	benign	0.054	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	N
T/N	0.2422	likely_benign	0.2837	benign	-1.007	Destabilizing	0.128	N	0.375	neutral	None	None	None	None	N
T/P	0.4361	ambiguous	0.4521	ambiguous	-0.306	Destabilizing	0.991	D	0.668	neutral	N	0.475829464	None	None	N
T/Q	0.7438	likely_pathogenic	0.7204	pathogenic	-0.848	Destabilizing	0.993	D	0.675	prob.neutral	None	None	None	None	N
T/R	0.7325	likely_pathogenic	0.715	pathogenic	-0.662	Destabilizing	0.982	D	0.649	neutral	D	0.523850123	None	None	N
T/S	0.2135	likely_benign	0.2242	benign	-1.296	Destabilizing	0.374	N	0.371	neutral	N	0.490505554	None	None	N
T/V	0.5803	likely_pathogenic	0.5374	ambiguous	-0.306	Destabilizing	0.976	D	0.571	neutral	None	None	None	None	N
T/W	0.958	likely_pathogenic	0.9492	pathogenic	-0.804	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
T/Y	0.8932	likely_pathogenic	0.8816	pathogenic	-0.466	Destabilizing	0.998	D	0.659	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.