TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18606	56041;56042;56043	chr2:178601088;178601087;178601086	chr2:179465815;179465814;179465813
N2AB	16965	51118;51119;51120	chr2:178601088;178601087;178601086	chr2:179465815;179465814;179465813
N2A	16038	48337;48338;48339	chr2:178601088;178601087;178601086	chr2:179465815;179465814;179465813
N2B	9541	28846;28847;28848	chr2:178601088;178601087;178601086	chr2:179465815;179465814;179465813
Novex-1	9666	29221;29222;29223	chr2:178601088;178601087;178601086	chr2:179465815;179465814;179465813
Novex-2	9733	29422;29423;29424	chr2:178601088;178601087;178601086	chr2:179465815;179465814;179465813
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-23
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.4746
• Predicted PPI site: I

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/N	None	None	0.543	N	0.261	0.214	0.250039746154	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62502E-06	0	0
D/V	None	None	0.999	N	0.719	0.567	0.730763679516	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
D/A	0.9123	likely_pathogenic	0.932	pathogenic	0.101	Stabilizing	0.994	D	0.631	neutral	N	0.482689091	None	None	I
D/C	0.9828	likely_pathogenic	0.9897	pathogenic	0.214	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/E	0.9203	likely_pathogenic	0.9409	pathogenic	-0.755	Destabilizing	0.989	D	0.51	neutral	N	0.482991806	None	None	I
D/F	0.9838	likely_pathogenic	0.9878	pathogenic	-0.402	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
D/G	0.8975	likely_pathogenic	0.9167	pathogenic	-0.162	Destabilizing	0.989	D	0.607	neutral	N	0.510708074	None	None	I
D/H	0.9143	likely_pathogenic	0.9368	pathogenic	-0.864	Destabilizing	0.595	D	0.479	neutral	N	0.502212151	None	None	I
D/I	0.9736	likely_pathogenic	0.9787	pathogenic	0.746	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
D/K	0.9772	likely_pathogenic	0.9833	pathogenic	0.04	Stabilizing	0.998	D	0.624	neutral	None	None	None	None	I
D/L	0.9652	likely_pathogenic	0.9713	pathogenic	0.746	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
D/M	0.9894	likely_pathogenic	0.9913	pathogenic	1.146	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/N	0.3208	likely_benign	0.3106	benign	-0.181	Destabilizing	0.543	D	0.261	neutral	N	0.507419233	None	None	I
D/P	0.9811	likely_pathogenic	0.9866	pathogenic	0.557	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	I
D/Q	0.9691	likely_pathogenic	0.9787	pathogenic	-0.095	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
D/R	0.9738	likely_pathogenic	0.9787	pathogenic	-0.165	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
D/S	0.6591	likely_pathogenic	0.6991	pathogenic	-0.33	Destabilizing	0.992	D	0.592	neutral	None	None	None	None	I
D/T	0.8322	likely_pathogenic	0.8679	pathogenic	-0.121	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	I
D/V	0.9353	likely_pathogenic	0.9487	pathogenic	0.557	Stabilizing	0.999	D	0.719	prob.delet.	N	0.501705172	None	None	I
D/W	0.9958	likely_pathogenic	0.9969	pathogenic	-0.591	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
D/Y	0.8776	likely_pathogenic	0.9141	pathogenic	-0.239	Destabilizing	0.997	D	0.725	prob.delet.	D	0.53720612	None	None	I

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.