TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25038	75337;75338;75339	chr2:178571020;178571019;178571018	chr2:179435747;179435746;179435745
N2AB	23397	70414;70415;70416	chr2:178571020;178571019;178571018	chr2:179435747;179435746;179435745
N2A	22470	67633;67634;67635	chr2:178571020;178571019;178571018	chr2:179435747;179435746;179435745
N2B	15973	48142;48143;48144	chr2:178571020;178571019;178571018	chr2:179435747;179435746;179435745
Novex-1	16098	48517;48518;48519	chr2:178571020;178571019;178571018	chr2:179435747;179435746;179435745
Novex-2	16165	48718;48719;48720	chr2:178571020;178571019;178571018	chr2:179435747;179435746;179435745
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: Fn3-70
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2184
• 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
I/S	None	None	0.942	D	0.817	0.53	0.813462614861	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
I/V	None	None	0.006	N	0.261	0.078	0.41219620536	gnomAD-4.0.0	1.36931E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31943E-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
I/A	0.9632	likely_pathogenic	0.9559	pathogenic	-2.332	Highly Destabilizing	0.754	D	0.663	neutral	None	None	None	None	I
I/C	0.9657	likely_pathogenic	0.9584	pathogenic	-1.663	Destabilizing	0.994	D	0.74	deleterious	None	None	None	None	I
I/D	0.9951	likely_pathogenic	0.9938	pathogenic	-2.534	Highly Destabilizing	0.993	D	0.85	deleterious	None	None	None	None	I
I/E	0.9877	likely_pathogenic	0.9843	pathogenic	-2.458	Highly Destabilizing	0.978	D	0.843	deleterious	None	None	None	None	I
I/F	0.8898	likely_pathogenic	0.863	pathogenic	-1.694	Destabilizing	0.942	D	0.742	deleterious	D	0.552022374	None	None	I
I/G	0.9915	likely_pathogenic	0.9887	pathogenic	-2.746	Highly Destabilizing	0.978	D	0.843	deleterious	None	None	None	None	I
I/H	0.9904	likely_pathogenic	0.988	pathogenic	-2.065	Highly Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	I
I/K	0.9826	likely_pathogenic	0.9779	pathogenic	-1.717	Destabilizing	0.978	D	0.842	deleterious	None	None	None	None	I
I/L	0.3446	ambiguous	0.3355	benign	-1.2	Destabilizing	0.294	N	0.439	neutral	N	0.484694235	None	None	I
I/M	0.4427	ambiguous	0.4272	ambiguous	-0.932	Destabilizing	0.942	D	0.707	prob.neutral	D	0.536453014	None	None	I
I/N	0.8425	likely_pathogenic	0.8365	pathogenic	-1.733	Destabilizing	0.99	D	0.848	deleterious	D	0.537466972	None	None	I
I/P	0.9573	likely_pathogenic	0.95	pathogenic	-1.552	Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	I
I/Q	0.9859	likely_pathogenic	0.9812	pathogenic	-1.857	Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	I
I/R	0.9804	likely_pathogenic	0.9752	pathogenic	-1.134	Destabilizing	0.978	D	0.848	deleterious	None	None	None	None	I
I/S	0.9615	likely_pathogenic	0.9497	pathogenic	-2.359	Highly Destabilizing	0.942	D	0.817	deleterious	D	0.543454453	None	None	I
I/T	0.9212	likely_pathogenic	0.906	pathogenic	-2.16	Highly Destabilizing	0.822	D	0.77	deleterious	N	0.516956407	None	None	I
I/V	0.1063	likely_benign	0.0976	benign	-1.552	Destabilizing	0.006	N	0.261	neutral	N	0.485353237	None	None	I
I/W	0.9959	likely_pathogenic	0.995	pathogenic	-1.931	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	I
I/Y	0.9748	likely_pathogenic	0.9674	pathogenic	-1.698	Destabilizing	0.978	D	0.783	deleterious	None	None	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.