TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20579	61960;61961;61962	chr2:178589990;178589989;178589988	chr2:179454717;179454716;179454715
N2AB	18938	57037;57038;57039	chr2:178589990;178589989;178589988	chr2:179454717;179454716;179454715
N2A	18011	54256;54257;54258	chr2:178589990;178589989;178589988	chr2:179454717;179454716;179454715
N2B	11514	34765;34766;34767	chr2:178589990;178589989;178589988	chr2:179454717;179454716;179454715
Novex-1	11639	35140;35141;35142	chr2:178589990;178589989;178589988	chr2:179454717;179454716;179454715
Novex-2	11706	35341;35342;35343	chr2:178589990;178589989;178589988	chr2:179454717;179454716;179454715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-37
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3285
• 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	0.497	N	0.63	0.187	0.225215365344	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	0.1066	likely_benign	0.1048	benign	-0.444	Destabilizing	0.055	N	0.407	neutral	N	0.508574026	None	None	N
T/C	0.4044	ambiguous	0.3793	ambiguous	-0.221	Destabilizing	0.909	D	0.668	neutral	None	None	None	None	N
T/D	0.5127	ambiguous	0.5175	ambiguous	-0.004	Destabilizing	0.157	N	0.601	neutral	None	None	None	None	N
T/E	0.4878	ambiguous	0.435	ambiguous	-0.079	Destabilizing	0.157	N	0.605	neutral	None	None	None	None	N
T/F	0.334	likely_benign	0.3239	benign	-0.899	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	N
T/G	0.2053	likely_benign	0.2398	benign	-0.588	Destabilizing	0.157	N	0.62	neutral	None	None	None	None	N
T/H	0.3634	ambiguous	0.3399	benign	-0.897	Destabilizing	0.909	D	0.73	prob.delet.	None	None	None	None	N
T/I	0.2865	likely_benign	0.2566	benign	-0.182	Destabilizing	0.497	N	0.63	neutral	N	0.471092523	None	None	N
T/K	0.4155	ambiguous	0.3483	ambiguous	-0.441	Destabilizing	0.157	N	0.6	neutral	None	None	None	None	N
T/L	0.1596	likely_benign	0.1433	benign	-0.182	Destabilizing	0.272	N	0.583	neutral	None	None	None	None	N
T/M	0.149	likely_benign	0.1287	benign	0.104	Stabilizing	0.968	D	0.679	prob.neutral	None	None	None	None	N
T/N	0.138	likely_benign	0.1487	benign	-0.208	Destabilizing	0.124	N	0.541	neutral	N	0.47803151	None	None	N
T/P	0.6794	likely_pathogenic	0.586	pathogenic	-0.24	Destabilizing	0.497	N	0.625	neutral	N	0.484387839	None	None	N
T/Q	0.3345	likely_benign	0.288	benign	-0.471	Destabilizing	0.567	D	0.685	prob.neutral	None	None	None	None	N
T/R	0.3911	ambiguous	0.3069	benign	-0.123	Destabilizing	0.567	D	0.674	neutral	None	None	None	None	N
T/S	0.0991	likely_benign	0.1118	benign	-0.416	Destabilizing	None	N	0.187	neutral	N	0.430667816	None	None	N
T/V	0.2079	likely_benign	0.1766	benign	-0.24	Destabilizing	0.272	N	0.509	neutral	None	None	None	None	N
T/W	0.7035	likely_pathogenic	0.6614	pathogenic	-0.882	Destabilizing	0.968	D	0.787	deleterious	None	None	None	None	N
T/Y	0.3817	ambiguous	0.3541	ambiguous	-0.615	Destabilizing	0.726	D	0.744	deleterious	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.