TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34944	105055;105056;105057	chr2:178531785;178531784;178531783	chr2:179396512;179396511;179396510
N2AB	33303	100132;100133;100134	chr2:178531785;178531784;178531783	chr2:179396512;179396511;179396510
N2A	32376	97351;97352;97353	chr2:178531785;178531784;178531783	chr2:179396512;179396511;179396510
N2B	25879	77860;77861;77862	chr2:178531785;178531784;178531783	chr2:179396512;179396511;179396510
Novex-1	26004	78235;78236;78237	chr2:178531785;178531784;178531783	chr2:179396512;179396511;179396510
Novex-2	26071	78436;78437;78438	chr2:178531785;178531784;178531783	chr2:179396512;179396511;179396510
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-163
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.148
• 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
I/V	rs367770867	-1.466	None	N	0.236	0.12	None	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
I/V	rs367770867	-1.466	None	N	0.236	0.12	None	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85753E-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
I/A	0.9849	likely_pathogenic	0.9885	pathogenic	-1.99	Destabilizing	0.072	N	0.712	prob.delet.	None	None	None	None	N
I/C	0.9843	likely_pathogenic	0.989	pathogenic	-1.143	Destabilizing	0.909	D	0.779	deleterious	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.999	pathogenic	-1.811	Destabilizing	0.726	D	0.883	deleterious	None	None	None	None	N
I/E	0.997	likely_pathogenic	0.9972	pathogenic	-1.791	Destabilizing	0.726	D	0.865	deleterious	None	None	None	None	N
I/F	0.6855	likely_pathogenic	0.7342	pathogenic	-1.419	Destabilizing	0.497	N	0.722	prob.delet.	N	0.368726428	None	None	N
I/G	0.9971	likely_pathogenic	0.9975	pathogenic	-2.344	Highly Destabilizing	0.726	D	0.861	deleterious	None	None	None	None	N
I/H	0.9956	likely_pathogenic	0.996	pathogenic	-1.647	Destabilizing	0.968	D	0.882	deleterious	None	None	None	None	N
I/K	0.9925	likely_pathogenic	0.9926	pathogenic	-1.438	Destabilizing	0.726	D	0.865	deleterious	None	None	None	None	N
I/L	0.5406	ambiguous	0.6077	pathogenic	-1.062	Destabilizing	0.025	N	0.418	neutral	N	0.486135176	None	None	N
I/M	0.4783	ambiguous	0.5325	ambiguous	-0.775	Destabilizing	0.497	N	0.697	prob.neutral	D	0.536083994	None	None	N
I/N	0.9817	likely_pathogenic	0.9824	pathogenic	-1.243	Destabilizing	0.859	D	0.888	deleterious	N	0.498666293	None	None	N
I/P	0.9906	likely_pathogenic	0.9898	pathogenic	-1.343	Destabilizing	0.726	D	0.887	deleterious	None	None	None	None	N
I/Q	0.9931	likely_pathogenic	0.9937	pathogenic	-1.432	Destabilizing	0.89	D	0.882	deleterious	None	None	None	None	N
I/R	0.9905	likely_pathogenic	0.9904	pathogenic	-0.827	Destabilizing	0.726	D	0.887	deleterious	None	None	None	None	N
I/S	0.9871	likely_pathogenic	0.9885	pathogenic	-1.818	Destabilizing	0.497	N	0.842	deleterious	N	0.498412804	None	None	N
I/T	0.9837	likely_pathogenic	0.988	pathogenic	-1.69	Destabilizing	0.124	N	0.725	prob.delet.	N	0.498159314	None	None	N
I/V	0.2341	likely_benign	0.3117	benign	-1.343	Destabilizing	None	N	0.236	neutral	N	0.469184211	None	None	N
I/W	0.9934	likely_pathogenic	0.9944	pathogenic	-1.549	Destabilizing	0.968	D	0.875	deleterious	None	None	None	None	N
I/Y	0.9716	likely_pathogenic	0.9729	pathogenic	-1.341	Destabilizing	0.726	D	0.794	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.