TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34304	103135;103136;103137	chr2:178533705;178533704;178533703	chr2:179398432;179398431;179398430
N2AB	32663	98212;98213;98214	chr2:178533705;178533704;178533703	chr2:179398432;179398431;179398430
N2A	31736	95431;95432;95433	chr2:178533705;178533704;178533703	chr2:179398432;179398431;179398430
N2B	25239	75940;75941;75942	chr2:178533705;178533704;178533703	chr2:179398432;179398431;179398430
Novex-1	25364	76315;76316;76317	chr2:178533705;178533704;178533703	chr2:179398432;179398431;179398430
Novex-2	25431	76516;76517;76518	chr2:178533705;178533704;178533703	chr2:179398432;179398431;179398430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-161
• Domain position: 47
• Structural Position: 113
• Q(SASA): 0.4246
• 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
D/E	None	None	0.004	N	0.27	0.067	0.0954503805726	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
D/N	rs1690185819	None	0.83	N	0.645	0.283	0.31077124679	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs1690185819	None	0.83	N	0.645	0.283	0.31077124679	gnomAD-4.0.0	6.57117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-05	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
D/A	0.1708	likely_benign	0.1463	benign	-0.126	Destabilizing	0.41	N	0.577	neutral	D	0.5282698	None	None	N
D/C	0.503	ambiguous	0.4757	ambiguous	0.304	Stabilizing	0.993	D	0.802	deleterious	None	None	None	None	N
D/E	0.1169	likely_benign	0.0969	benign	-0.253	Destabilizing	0.004	N	0.27	neutral	N	0.497773535	None	None	N
D/F	0.5533	ambiguous	0.4776	ambiguous	-0.29	Destabilizing	0.993	D	0.795	deleterious	None	None	None	None	N
D/G	0.1275	likely_benign	0.1082	benign	-0.313	Destabilizing	0.581	D	0.573	neutral	N	0.513281705	None	None	N
D/H	0.2242	likely_benign	0.1952	benign	-0.344	Destabilizing	0.974	D	0.72	prob.delet.	D	0.526347002	None	None	N
D/I	0.3298	likely_benign	0.2715	benign	0.311	Stabilizing	0.929	D	0.793	deleterious	None	None	None	None	N
D/K	0.2611	likely_benign	0.1959	benign	0.415	Stabilizing	0.764	D	0.642	neutral	None	None	None	None	N
D/L	0.3277	likely_benign	0.2642	benign	0.311	Stabilizing	0.866	D	0.761	deleterious	None	None	None	None	N
D/M	0.5644	likely_pathogenic	0.4843	ambiguous	0.548	Stabilizing	0.993	D	0.789	deleterious	None	None	None	None	N
D/N	0.0937	likely_benign	0.0851	benign	0.257	Stabilizing	0.83	D	0.645	neutral	N	0.448270221	None	None	N
D/P	0.467	ambiguous	0.3925	ambiguous	0.188	Stabilizing	0.929	D	0.667	neutral	None	None	None	None	N
D/Q	0.2518	likely_benign	0.1978	benign	0.276	Stabilizing	0.764	D	0.697	prob.neutral	None	None	None	None	N
D/R	0.2881	likely_benign	0.2366	benign	0.409	Stabilizing	0.764	D	0.715	prob.delet.	None	None	None	None	N
D/S	0.1116	likely_benign	0.0961	benign	0.147	Stabilizing	0.48	N	0.508	neutral	None	None	None	None	N
D/T	0.2189	likely_benign	0.1772	benign	0.286	Stabilizing	0.866	D	0.656	neutral	None	None	None	None	N
D/V	0.2277	likely_benign	0.1964	benign	0.188	Stabilizing	0.83	D	0.752	deleterious	N	0.514495213	None	None	N
D/W	0.7996	likely_pathogenic	0.7594	pathogenic	-0.256	Destabilizing	0.993	D	0.804	deleterious	None	None	None	None	N
D/Y	0.2255	likely_benign	0.2091	benign	-0.076	Destabilizing	0.991	D	0.794	deleterious	N	0.515209931	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.