TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31371	94336;94337;94338	chr2:178547515;178547514;178547513	chr2:179412242;179412241;179412240
N2AB	29730	89413;89414;89415	chr2:178547515;178547514;178547513	chr2:179412242;179412241;179412240
N2A	28803	86632;86633;86634	chr2:178547515;178547514;178547513	chr2:179412242;179412241;179412240
N2B	22306	67141;67142;67143	chr2:178547515;178547514;178547513	chr2:179412242;179412241;179412240
Novex-1	22431	67516;67517;67518	chr2:178547515;178547514;178547513	chr2:179412242;179412241;179412240
Novex-2	22498	67717;67718;67719	chr2:178547515;178547514;178547513	chr2:179412242;179412241;179412240
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-116
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4242
• 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	rs767255232	0.116	0.964	N	0.656	0.344	0.519889284407	gnomAD-4.0.0	5.47441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19603E-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	0.1479	likely_benign	0.1317	benign	-0.603	Destabilizing	0.76	D	0.483	neutral	D	0.524178197	None	None	N
T/C	0.5074	ambiguous	0.4728	ambiguous	-0.342	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
T/D	0.7639	likely_pathogenic	0.7448	pathogenic	0.121	Stabilizing	0.986	D	0.656	neutral	None	None	None	None	N
T/E	0.7444	likely_pathogenic	0.7358	pathogenic	0.097	Stabilizing	0.986	D	0.651	neutral	None	None	None	None	N
T/F	0.4945	ambiguous	0.468	ambiguous	-0.764	Destabilizing	0.986	D	0.743	deleterious	None	None	None	None	N
T/G	0.2843	likely_benign	0.2616	benign	-0.826	Destabilizing	0.91	D	0.618	neutral	None	None	None	None	N
T/H	0.5033	ambiguous	0.445	ambiguous	-1.02	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
T/I	0.3615	ambiguous	0.3534	ambiguous	-0.112	Destabilizing	0.964	D	0.656	neutral	N	0.474285755	None	None	N
T/K	0.5609	ambiguous	0.5438	ambiguous	-0.58	Destabilizing	0.986	D	0.657	neutral	None	None	None	None	N
T/L	0.1656	likely_benign	0.1418	benign	-0.112	Destabilizing	0.778	D	0.513	neutral	None	None	None	None	N
T/M	0.1186	likely_benign	0.1113	benign	0.05	Stabilizing	0.807	D	0.413	neutral	None	None	None	None	N
T/N	0.1904	likely_benign	0.1739	benign	-0.418	Destabilizing	0.982	D	0.572	neutral	N	0.472004349	None	None	N
T/P	0.1309	likely_benign	0.1123	benign	-0.244	Destabilizing	0.991	D	0.717	prob.delet.	N	0.477232399	None	None	N
T/Q	0.4572	ambiguous	0.4174	ambiguous	-0.573	Destabilizing	0.993	D	0.72	prob.delet.	None	None	None	None	N
T/R	0.5318	ambiguous	0.5097	ambiguous	-0.313	Destabilizing	0.986	D	0.717	prob.delet.	None	None	None	None	N
T/S	0.1465	likely_benign	0.1249	benign	-0.701	Destabilizing	0.17	N	0.361	neutral	N	0.452507313	None	None	N
T/V	0.2653	likely_benign	0.2479	benign	-0.244	Destabilizing	0.91	D	0.461	neutral	None	None	None	None	N
T/W	0.7948	likely_pathogenic	0.781	pathogenic	-0.729	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
T/Y	0.5296	ambiguous	0.4945	ambiguous	-0.491	Destabilizing	0.993	D	0.749	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.