TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9166	27721;27722;27723	chr2:178712426;178712425;178712424	chr2:179577153;179577152;179577151
N2AB	8849	26770;26771;26772	chr2:178712426;178712425;178712424	chr2:179577153;179577152;179577151
N2A	7922	23989;23990;23991	chr2:178712426;178712425;178712424	chr2:179577153;179577152;179577151
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCG
• RefSeq wild type template codon: AGC
• Domain: Ig-77
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1803
• 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
S/L	rs773637100	-0.337	0.996	D	0.641	0.457	0.739841096875	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
S/L	rs773637100	-0.337	0.996	D	0.641	0.457	0.739841096875	gnomAD-4.0.0	3.42096E-06	None	None	None	None	N	None	2.98775E-05	0	None	0	0	None	0	0	3.59778E-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
S/A	0.1171	likely_benign	0.1203	benign	-0.918	Destabilizing	0.948	D	0.455	neutral	N	0.489251182	None	None	N
S/C	0.2299	likely_benign	0.2052	benign	-0.693	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/D	0.7888	likely_pathogenic	0.8309	pathogenic	-0.521	Destabilizing	0.992	D	0.631	neutral	None	None	None	None	N
S/E	0.8071	likely_pathogenic	0.8436	pathogenic	-0.472	Destabilizing	0.992	D	0.615	neutral	None	None	None	None	N
S/F	0.347	ambiguous	0.3856	ambiguous	-1.025	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
S/G	0.2121	likely_benign	0.2222	benign	-1.201	Destabilizing	0.992	D	0.497	neutral	None	None	None	None	N
S/H	0.598	likely_pathogenic	0.6282	pathogenic	-1.61	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
S/I	0.3345	likely_benign	0.3543	ambiguous	-0.255	Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	N
S/K	0.896	likely_pathogenic	0.919	pathogenic	-0.576	Destabilizing	0.983	D	0.622	neutral	None	None	None	None	N
S/L	0.1565	likely_benign	0.1653	benign	-0.255	Destabilizing	0.996	D	0.641	neutral	D	0.533886263	None	None	N
S/M	0.2654	likely_benign	0.2705	benign	-0.056	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/N	0.3053	likely_benign	0.3379	benign	-0.717	Destabilizing	0.992	D	0.606	neutral	None	None	None	None	N
S/P	0.9632	likely_pathogenic	0.9662	pathogenic	-0.443	Destabilizing	0.999	D	0.771	deleterious	N	0.506825686	None	None	N
S/Q	0.761	likely_pathogenic	0.7908	pathogenic	-0.82	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
S/R	0.8577	likely_pathogenic	0.8832	pathogenic	-0.575	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
S/T	0.0925	likely_benign	0.0987	benign	-0.699	Destabilizing	0.37	N	0.389	neutral	N	0.461292659	None	None	N
S/V	0.2994	likely_benign	0.3125	benign	-0.443	Destabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	N
S/W	0.5715	likely_pathogenic	0.5728	pathogenic	-1.002	Destabilizing	1.0	D	0.73	prob.delet.	N	0.515726456	None	None	N
S/Y	0.2668	likely_benign	0.2921	benign	-0.703	Destabilizing	0.999	D	0.758	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.