TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24522	73789;73790;73791	chr2:178572568;178572567;178572566	chr2:179437295;179437294;179437293
N2AB	22881	68866;68867;68868	chr2:178572568;178572567;178572566	chr2:179437295;179437294;179437293
N2A	21954	66085;66086;66087	chr2:178572568;178572567;178572566	chr2:179437295;179437294;179437293
N2B	15457	46594;46595;46596	chr2:178572568;178572567;178572566	chr2:179437295;179437294;179437293
Novex-1	15582	46969;46970;46971	chr2:178572568;178572567;178572566	chr2:179437295;179437294;179437293
Novex-2	15649	47170;47171;47172	chr2:178572568;178572567;178572566	chr2:179437295;179437294;179437293
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-66
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2215
• 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
P/A	rs1195696847	-1.712	0.001	N	0.449	0.167	0.212008924253	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/A	rs1195696847	-1.712	0.001	N	0.449	0.167	0.212008924253	gnomAD-4.0.0	1.59198E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	0	0	0
P/R	None	None	0.993	N	0.836	0.447	0.551177841964	gnomAD-4.0.0	1.59202E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43303E-05	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
P/A	0.0769	likely_benign	0.0649	benign	-1.587	Destabilizing	0.001	N	0.449	neutral	N	0.446191842	None	None	N
P/C	0.5049	ambiguous	0.4145	ambiguous	-0.943	Destabilizing	0.982	D	0.833	deleterious	None	None	None	None	N
P/D	0.8508	likely_pathogenic	0.767	pathogenic	-1.594	Destabilizing	0.78	D	0.785	deleterious	None	None	None	None	N
P/E	0.5333	ambiguous	0.426	ambiguous	-1.612	Destabilizing	0.442	N	0.777	deleterious	None	None	None	None	N
P/F	0.6699	likely_pathogenic	0.5549	ambiguous	-1.282	Destabilizing	0.994	D	0.853	deleterious	None	None	None	None	N
P/G	0.4762	ambiguous	0.3857	ambiguous	-1.892	Destabilizing	0.719	D	0.768	deleterious	None	None	None	None	N
P/H	0.424	ambiguous	0.3143	benign	-1.438	Destabilizing	0.998	D	0.822	deleterious	D	0.525876268	None	None	N
P/I	0.4341	ambiguous	0.3315	benign	-0.847	Destabilizing	0.989	D	0.829	deleterious	None	None	None	None	N
P/K	0.4892	ambiguous	0.3695	ambiguous	-1.31	Destabilizing	0.962	D	0.779	deleterious	None	None	None	None	N
P/L	0.2314	likely_benign	0.1685	benign	-0.847	Destabilizing	0.95	D	0.809	deleterious	N	0.517228988	None	None	N
P/M	0.391	ambiguous	0.3092	benign	-0.552	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
P/N	0.6207	likely_pathogenic	0.5112	ambiguous	-1.033	Destabilizing	0.957	D	0.839	deleterious	None	None	None	None	N
P/Q	0.2994	likely_benign	0.2009	benign	-1.255	Destabilizing	0.985	D	0.771	deleterious	None	None	None	None	N
P/R	0.3936	ambiguous	0.2686	benign	-0.728	Destabilizing	0.993	D	0.836	deleterious	N	0.501478136	None	None	N
P/S	0.1987	likely_benign	0.1454	benign	-1.514	Destabilizing	0.727	D	0.745	deleterious	N	0.487386352	None	None	N
P/T	0.2352	likely_benign	0.161	benign	-1.434	Destabilizing	0.703	D	0.759	deleterious	N	0.51359491	None	None	N
P/V	0.2984	likely_benign	0.2243	benign	-1.06	Destabilizing	0.689	D	0.785	deleterious	None	None	None	None	N
P/W	0.8777	likely_pathogenic	0.7889	pathogenic	-1.46	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/Y	0.6688	likely_pathogenic	0.5606	ambiguous	-1.203	Destabilizing	0.998	D	0.854	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.