TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24784	74575;74576;74577	chr2:178571782;178571781;178571780	chr2:179436509;179436508;179436507
N2AB	23143	69652;69653;69654	chr2:178571782;178571781;178571780	chr2:179436509;179436508;179436507
N2A	22216	66871;66872;66873	chr2:178571782;178571781;178571780	chr2:179436509;179436508;179436507
N2B	15719	47380;47381;47382	chr2:178571782;178571781;178571780	chr2:179436509;179436508;179436507
Novex-1	15844	47755;47756;47757	chr2:178571782;178571781;178571780	chr2:179436509;179436508;179436507
Novex-2	15911	47956;47957;47958	chr2:178571782;178571781;178571780	chr2:179436509;179436508;179436507
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-133
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2235
• 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
G/D	None	None	0.997	D	0.851	0.816	0.662036563411	gnomAD-4.0.0	4.77613E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85981E-06	2.86714E-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
G/A	0.6406	likely_pathogenic	0.6485	pathogenic	-0.84	Destabilizing	0.995	D	0.793	deleterious	D	0.580041519	None	None	I
G/C	0.8659	likely_pathogenic	0.8746	pathogenic	-0.717	Destabilizing	1.0	D	0.789	deleterious	D	0.653676997	None	None	I
G/D	0.9057	likely_pathogenic	0.9179	pathogenic	-1.749	Destabilizing	0.997	D	0.851	deleterious	D	0.637021863	None	None	I
G/E	0.9621	likely_pathogenic	0.9672	pathogenic	-1.765	Destabilizing	0.822	D	0.734	prob.delet.	None	None	None	None	I
G/F	0.9904	likely_pathogenic	0.9911	pathogenic	-1.086	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
G/H	0.9862	likely_pathogenic	0.9881	pathogenic	-1.738	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/I	0.9906	likely_pathogenic	0.9915	pathogenic	-0.293	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/K	0.9899	likely_pathogenic	0.9914	pathogenic	-1.426	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	I
G/L	0.9838	likely_pathogenic	0.9842	pathogenic	-0.293	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	I
G/M	0.9904	likely_pathogenic	0.9905	pathogenic	-0.047	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
G/N	0.9477	likely_pathogenic	0.9555	pathogenic	-1.103	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	I
G/P	0.9989	likely_pathogenic	0.9991	pathogenic	-0.434	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	I
G/Q	0.9691	likely_pathogenic	0.9717	pathogenic	-1.228	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	I
G/R	0.9714	likely_pathogenic	0.9737	pathogenic	-1.164	Destabilizing	0.999	D	0.847	deleterious	D	0.653475193	None	None	I
G/S	0.5492	ambiguous	0.5699	pathogenic	-1.308	Destabilizing	0.999	D	0.873	deleterious	D	0.620800698	None	None	I
G/T	0.934	likely_pathogenic	0.9429	pathogenic	-1.256	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	I
G/V	0.9764	likely_pathogenic	0.9789	pathogenic	-0.434	Destabilizing	0.999	D	0.82	deleterious	D	0.637425472	None	None	I
G/W	0.9849	likely_pathogenic	0.9868	pathogenic	-1.62	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/Y	0.9882	likely_pathogenic	0.9888	pathogenic	-1.18	Destabilizing	1.0	D	0.823	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.