TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17686	53281;53282;53283	chr2:178607632;178607631;178607630	chr2:179472359;179472358;179472357
N2AB	16045	48358;48359;48360	chr2:178607632;178607631;178607630	chr2:179472359;179472358;179472357
N2A	15118	45577;45578;45579	chr2:178607632;178607631;178607630	chr2:179472359;179472358;179472357
N2B	8621	26086;26087;26088	chr2:178607632;178607631;178607630	chr2:179472359;179472358;179472357
Novex-1	8746	26461;26462;26463	chr2:178607632;178607631;178607630	chr2:179472359;179472358;179472357
Novex-2	8813	26662;26663;26664	chr2:178607632;178607631;178607630	chr2:179472359;179472358;179472357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-113
• Domain position: 10
• Structural Position: 23
• Q(SASA): 0.3559
• 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
A/S	rs1576364760	None	0.998	N	0.551	0.252	0.16115917748	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94553E-04	None	0	0	0	0	0
A/S	rs1576364760	None	0.998	N	0.551	0.252	0.16115917748	gnomAD-4.0.0	3.84634E-06	None	None	None	None	N	None	0	0	None	0	2.43202E-05	None	0	0	0	2.68082E-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
A/C	0.8323	likely_pathogenic	0.8669	pathogenic	-0.759	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/D	0.9646	likely_pathogenic	0.9691	pathogenic	-1.137	Destabilizing	1.0	D	0.731	prob.delet.	N	0.471291608	None	None	N
A/E	0.909	likely_pathogenic	0.9238	pathogenic	-1.232	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/F	0.9532	likely_pathogenic	0.9624	pathogenic	-1.103	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
A/G	0.6221	likely_pathogenic	0.6674	pathogenic	-0.984	Destabilizing	0.999	D	0.566	neutral	N	0.492941035	None	None	N
A/H	0.9516	likely_pathogenic	0.9542	pathogenic	-1.124	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
A/I	0.818	likely_pathogenic	0.8597	pathogenic	-0.49	Destabilizing	0.994	D	0.649	neutral	None	None	None	None	N
A/K	0.9454	likely_pathogenic	0.9534	pathogenic	-1.227	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
A/L	0.8132	likely_pathogenic	0.8485	pathogenic	-0.49	Destabilizing	0.994	D	0.513	neutral	None	None	None	None	N
A/M	0.8269	likely_pathogenic	0.8598	pathogenic	-0.316	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
A/N	0.8689	likely_pathogenic	0.8737	pathogenic	-0.807	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
A/P	0.9379	likely_pathogenic	0.9593	pathogenic	-0.556	Destabilizing	1.0	D	0.731	prob.delet.	N	0.461225523	None	None	N
A/Q	0.8672	likely_pathogenic	0.8712	pathogenic	-1.06	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/R	0.8809	likely_pathogenic	0.8986	pathogenic	-0.732	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
A/S	0.2724	likely_benign	0.3112	benign	-1.058	Destabilizing	0.998	D	0.551	neutral	N	0.510485676	None	None	N
A/T	0.5532	ambiguous	0.6377	pathogenic	-1.076	Destabilizing	0.996	D	0.665	neutral	N	0.461225523	None	None	N
A/V	0.4313	ambiguous	0.5094	ambiguous	-0.556	Destabilizing	0.884	D	0.375	neutral	N	0.499881893	None	None	N
A/W	0.9916	likely_pathogenic	0.9933	pathogenic	-1.356	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/Y	0.9648	likely_pathogenic	0.9681	pathogenic	-1.011	Destabilizing	1.0	D	0.769	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.