TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16241	48946;48947;48948	chr2:178614886;178614885;178614884	chr2:179479613;179479612;179479611
N2AB	14600	44023;44024;44025	chr2:178614886;178614885;178614884	chr2:179479613;179479612;179479611
N2A	13673	41242;41243;41244	chr2:178614886;178614885;178614884	chr2:179479613;179479612;179479611
N2B	7176	21751;21752;21753	chr2:178614886;178614885;178614884	chr2:179479613;179479612;179479611
Novex-1	7301	22126;22127;22128	chr2:178614886;178614885;178614884	chr2:179479613;179479612;179479611
Novex-2	7368	22327;22328;22329	chr2:178614886;178614885;178614884	chr2:179479613;179479612;179479611
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-5
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1526
• 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/N	None	None	0.211	D	0.783	0.406	0.315314060047	gnomAD-4.0.0	2.1041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7463E-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	0.3361	likely_benign	0.2411	benign	-0.591	Destabilizing	0.016	N	0.611	neutral	None	None	None	None	N
S/C	0.2509	likely_benign	0.1817	benign	-0.552	Destabilizing	None	N	0.599	neutral	D	0.75120934	None	None	N
S/D	0.9798	likely_pathogenic	0.9698	pathogenic	-1.078	Destabilizing	0.519	D	0.787	deleterious	None	None	None	None	N
S/E	0.9916	likely_pathogenic	0.9875	pathogenic	-0.985	Destabilizing	0.519	D	0.793	deleterious	None	None	None	None	N
S/F	0.9824	likely_pathogenic	0.954	pathogenic	-0.296	Destabilizing	0.555	D	0.836	deleterious	None	None	None	None	N
S/G	0.3748	ambiguous	0.2836	benign	-0.932	Destabilizing	0.117	N	0.744	deleterious	D	0.660145157	None	None	N
S/H	0.9763	likely_pathogenic	0.9623	pathogenic	-1.433	Destabilizing	0.935	D	0.808	deleterious	None	None	None	None	N
S/I	0.9595	likely_pathogenic	0.8871	pathogenic	0.238	Stabilizing	0.317	N	0.844	deleterious	D	0.728411945	None	None	N
S/K	0.9981	likely_pathogenic	0.9973	pathogenic	-0.967	Destabilizing	0.262	N	0.785	deleterious	None	None	None	None	N
S/L	0.8917	likely_pathogenic	0.7776	pathogenic	0.238	Stabilizing	0.081	N	0.806	deleterious	None	None	None	None	N
S/M	0.9408	likely_pathogenic	0.8864	pathogenic	0.249	Stabilizing	0.791	D	0.813	deleterious	None	None	None	None	N
S/N	0.8995	likely_pathogenic	0.8426	pathogenic	-1.178	Destabilizing	0.211	N	0.783	deleterious	D	0.785228913	None	None	N
S/P	0.9895	likely_pathogenic	0.9814	pathogenic	-0.003	Destabilizing	0.791	D	0.825	deleterious	None	None	None	None	N
S/Q	0.9833	likely_pathogenic	0.9774	pathogenic	-1.089	Destabilizing	0.791	D	0.763	deleterious	None	None	None	None	N
S/R	0.9939	likely_pathogenic	0.9919	pathogenic	-1.101	Destabilizing	0.741	D	0.822	deleterious	D	0.660145157	None	None	N
S/T	0.498	ambiguous	0.3946	ambiguous	-0.948	Destabilizing	0.117	N	0.739	prob.delet.	D	0.582461722	None	None	N
S/V	0.8892	likely_pathogenic	0.7647	pathogenic	-0.003	Destabilizing	0.081	N	0.818	deleterious	None	None	None	None	N
S/W	0.9878	likely_pathogenic	0.9743	pathogenic	-0.499	Destabilizing	0.935	D	0.87	deleterious	None	None	None	None	N
S/Y	0.9766	likely_pathogenic	0.9469	pathogenic	-0.174	Destabilizing	0.791	D	0.843	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.