TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25587	76984;76985;76986	chr2:178569373;178569372;178569371	chr2:179434100;179434099;179434098
N2AB	23946	72061;72062;72063	chr2:178569373;178569372;178569371	chr2:179434100;179434099;179434098
N2A	23019	69280;69281;69282	chr2:178569373;178569372;178569371	chr2:179434100;179434099;179434098
N2B	16522	49789;49790;49791	chr2:178569373;178569372;178569371	chr2:179434100;179434099;179434098
Novex-1	16647	50164;50165;50166	chr2:178569373;178569372;178569371	chr2:179434100;179434099;179434098
Novex-2	16714	50365;50366;50367	chr2:178569373;178569372;178569371	chr2:179434100;179434099;179434098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-135
• Domain position: 74
• Structural Position: 163
• Q(SASA): 0.5886
• 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
S/N	None	None	0.722	D	0.505	0.286	0.29385284311	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
S/A	0.0759	likely_benign	0.07	benign	-0.306	Destabilizing	0.415	N	0.524	neutral	None	None	None	None	I
S/C	0.0735	likely_benign	0.0705	benign	-0.392	Destabilizing	0.995	D	0.569	neutral	N	0.498836742	None	None	I
S/D	0.7648	likely_pathogenic	0.7769	pathogenic	-0.168	Destabilizing	0.775	D	0.471	neutral	None	None	None	None	I
S/E	0.806	likely_pathogenic	0.8041	pathogenic	-0.277	Destabilizing	0.775	D	0.493	neutral	None	None	None	None	I
S/F	0.3051	likely_benign	0.2584	benign	-1.076	Destabilizing	0.987	D	0.639	neutral	None	None	None	None	I
S/G	0.1201	likely_benign	0.1454	benign	-0.303	Destabilizing	0.008	N	0.344	neutral	D	0.530595242	None	None	I
S/H	0.51	ambiguous	0.5023	ambiguous	-0.644	Destabilizing	0.989	D	0.535	neutral	None	None	None	None	I
S/I	0.1936	likely_benign	0.181	benign	-0.426	Destabilizing	0.949	D	0.633	neutral	N	0.511566764	None	None	I
S/K	0.86	likely_pathogenic	0.864	pathogenic	-0.395	Destabilizing	0.633	D	0.481	neutral	None	None	None	None	I
S/L	0.1301	likely_benign	0.1124	benign	-0.426	Destabilizing	0.775	D	0.554	neutral	None	None	None	None	I
S/M	0.254	likely_benign	0.2439	benign	-0.253	Destabilizing	0.996	D	0.55	neutral	None	None	None	None	I
S/N	0.2801	likely_benign	0.2718	benign	-0.178	Destabilizing	0.722	D	0.505	neutral	D	0.523997344	None	None	I
S/P	0.8639	likely_pathogenic	0.8642	pathogenic	-0.368	Destabilizing	0.987	D	0.523	neutral	None	None	None	None	I
S/Q	0.6864	likely_pathogenic	0.6893	pathogenic	-0.393	Destabilizing	0.923	D	0.511	neutral	None	None	None	None	I
S/R	0.7662	likely_pathogenic	0.7658	pathogenic	-0.208	Destabilizing	0.018	N	0.495	neutral	N	0.491581813	None	None	I
S/T	0.1288	likely_benign	0.1223	benign	-0.297	Destabilizing	0.722	D	0.497	neutral	D	0.52972845	None	None	I
S/V	0.1769	likely_benign	0.1634	benign	-0.368	Destabilizing	0.961	D	0.589	neutral	None	None	None	None	I
S/W	0.5685	likely_pathogenic	0.53	ambiguous	-1.158	Destabilizing	0.996	D	0.692	prob.neutral	None	None	None	None	I
S/Y	0.3358	likely_benign	0.2928	benign	-0.864	Destabilizing	0.987	D	0.637	neutral	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.