TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25557	76894;76895;76896	chr2:178569463;178569462;178569461	chr2:179434190;179434189;179434188
N2AB	23916	71971;71972;71973	chr2:178569463;178569462;178569461	chr2:179434190;179434189;179434188
N2A	22989	69190;69191;69192	chr2:178569463;178569462;178569461	chr2:179434190;179434189;179434188
N2B	16492	49699;49700;49701	chr2:178569463;178569462;178569461	chr2:179434190;179434189;179434188
Novex-1	16617	50074;50075;50076	chr2:178569463;178569462;178569461	chr2:179434190;179434189;179434188
Novex-2	16684	50275;50276;50277	chr2:178569463;178569462;178569461	chr2:179434190;179434189;179434188
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-135
• Domain position: 44
• Structural Position: 123
• Q(SASA): 0.3172
• 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/T	rs758441370	-1.942	0.822	N	0.497	0.466	0.723066985631	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.91E-06	0
I/T	rs758441370	-1.942	0.822	N	0.497	0.466	0.723066985631	gnomAD-4.0.0	3.42287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69952E-06	2.32035E-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	0.4397	ambiguous	0.5054	ambiguous	-1.714	Destabilizing	0.86	D	0.505	neutral	None	None	None	None	N
I/C	0.8386	likely_pathogenic	0.8631	pathogenic	-1.126	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
I/D	0.954	likely_pathogenic	0.9632	pathogenic	-1.168	Destabilizing	0.993	D	0.714	prob.delet.	None	None	None	None	N
I/E	0.8203	likely_pathogenic	0.8409	pathogenic	-1.118	Destabilizing	0.978	D	0.7	prob.neutral	None	None	None	None	N
I/F	0.3304	likely_benign	0.3497	ambiguous	-1.118	Destabilizing	0.698	D	0.415	neutral	N	0.490465723	None	None	N
I/G	0.8852	likely_pathogenic	0.9135	pathogenic	-2.077	Highly Destabilizing	0.978	D	0.699	prob.neutral	None	None	None	None	N
I/H	0.8169	likely_pathogenic	0.8375	pathogenic	-1.18	Destabilizing	0.988	D	0.709	prob.delet.	None	None	None	None	N
I/K	0.5992	likely_pathogenic	0.6273	pathogenic	-1.219	Destabilizing	0.978	D	0.701	prob.neutral	None	None	None	None	N
I/L	0.1929	likely_benign	0.2053	benign	-0.771	Destabilizing	0.294	N	0.397	neutral	N	0.485110125	None	None	N
I/M	0.1385	likely_benign	0.1417	benign	-0.685	Destabilizing	0.97	D	0.491	neutral	N	0.489379767	None	None	N
I/N	0.6956	likely_pathogenic	0.7279	pathogenic	-1.162	Destabilizing	0.97	D	0.725	prob.delet.	D	0.547010668	None	None	N
I/P	0.918	likely_pathogenic	0.9429	pathogenic	-1.055	Destabilizing	0.993	D	0.723	prob.delet.	None	None	None	None	N
I/Q	0.6881	likely_pathogenic	0.7211	pathogenic	-1.255	Destabilizing	0.978	D	0.719	prob.delet.	None	None	None	None	N
I/R	0.5064	ambiguous	0.531	ambiguous	-0.669	Destabilizing	0.978	D	0.722	prob.delet.	None	None	None	None	N
I/S	0.5459	ambiguous	0.6026	pathogenic	-1.795	Destabilizing	0.97	D	0.633	neutral	N	0.506750007	None	None	N
I/T	0.1546	likely_benign	0.1833	benign	-1.612	Destabilizing	0.822	D	0.497	neutral	N	0.504761771	None	None	N
I/V	0.085	likely_benign	0.0901	benign	-1.055	Destabilizing	0.058	N	0.186	neutral	N	0.498040106	None	None	N
I/W	0.8945	likely_pathogenic	0.9096	pathogenic	-1.213	Destabilizing	0.994	D	0.733	prob.delet.	None	None	None	None	N
I/Y	0.7963	likely_pathogenic	0.8202	pathogenic	-0.981	Destabilizing	0.043	N	0.317	neutral	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.