TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13901	41926;41927;41928	chr2:178635623;178635622;178635621	chr2:179500350;179500349;179500348
N2AB	12260	37003;37004;37005	chr2:178635623;178635622;178635621	chr2:179500350;179500349;179500348
N2A	11333	34222;34223;34224	chr2:178635623;178635622;178635621	chr2:179500350;179500349;179500348
N2B	4836	14731;14732;14733	chr2:178635623;178635622;178635621	chr2:179500350;179500349;179500348
Novex-1	4961	15106;15107;15108	chr2:178635623;178635622;178635621	chr2:179500350;179500349;179500348
Novex-2	5028	15307;15308;15309	chr2:178635623;178635622;178635621	chr2:179500350;179500349;179500348
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: Ig-89
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.4415
• 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/P	None	None	1.0	N	0.683	0.43	0.322510055762	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
T/S	None	None	0.816	N	0.349	0.195	0.203808441222	gnomAD-4.0.0	1.64096E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94488E-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	0.4714	ambiguous	0.4451	ambiguous	-0.567	Destabilizing	0.959	D	0.449	neutral	N	0.49481264	None	None	N
T/C	0.899	likely_pathogenic	0.904	pathogenic	-0.362	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.9747	likely_pathogenic	0.9633	pathogenic	-0.016	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
T/E	0.9706	likely_pathogenic	0.9555	pathogenic	-0.017	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
T/F	0.938	likely_pathogenic	0.8956	pathogenic	-0.705	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
T/G	0.8393	likely_pathogenic	0.8192	pathogenic	-0.813	Destabilizing	0.993	D	0.601	neutral	None	None	None	None	N
T/H	0.8959	likely_pathogenic	0.8758	pathogenic	-1.075	Destabilizing	1.0	D	0.739	deleterious	None	None	None	None	N
T/I	0.8141	likely_pathogenic	0.7238	pathogenic	-0.009	Destabilizing	0.999	D	0.673	prob.neutral	N	0.499392542	None	None	N
T/K	0.9259	likely_pathogenic	0.8892	pathogenic	-0.624	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
T/L	0.613	likely_pathogenic	0.5084	ambiguous	-0.009	Destabilizing	0.997	D	0.594	neutral	None	None	None	None	N
T/M	0.5744	likely_pathogenic	0.4727	ambiguous	0.061	Stabilizing	1.0	D	0.692	prob.delet.	None	None	None	None	N
T/N	0.7498	likely_pathogenic	0.6916	pathogenic	-0.534	Destabilizing	0.997	D	0.633	neutral	N	0.443968219	None	None	N
T/P	0.7918	likely_pathogenic	0.7035	pathogenic	-0.162	Destabilizing	1.0	D	0.683	prob.neutral	N	0.493168374	None	None	N
T/Q	0.9239	likely_pathogenic	0.9017	pathogenic	-0.616	Destabilizing	0.999	D	0.656	prob.neutral	None	None	None	None	N
T/R	0.9269	likely_pathogenic	0.8986	pathogenic	-0.442	Destabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	N
T/S	0.478	ambiguous	0.4717	ambiguous	-0.765	Destabilizing	0.816	D	0.349	neutral	N	0.495992709	None	None	N
T/V	0.6368	likely_pathogenic	0.5781	pathogenic	-0.162	Destabilizing	0.997	D	0.563	neutral	None	None	None	None	N
T/W	0.9903	likely_pathogenic	0.9839	pathogenic	-0.728	Destabilizing	1.0	D	0.724	deleterious	None	None	None	None	N
T/Y	0.9508	likely_pathogenic	0.9213	pathogenic	-0.465	Destabilizing	1.0	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.