TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18058	54397;54398;54399	chr2:178605005;178605004;178605003	chr2:179469732;179469731;179469730
N2AB	16417	49474;49475;49476	chr2:178605005;178605004;178605003	chr2:179469732;179469731;179469730
N2A	15490	46693;46694;46695	chr2:178605005;178605004;178605003	chr2:179469732;179469731;179469730
N2B	8993	27202;27203;27204	chr2:178605005;178605004;178605003	chr2:179469732;179469731;179469730
Novex-1	9118	27577;27578;27579	chr2:178605005;178605004;178605003	chr2:179469732;179469731;179469730
Novex-2	9185	27778;27779;27780	chr2:178605005;178605004;178605003	chr2:179469732;179469731;179469730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-114
• Domain position: 91
• Structural Position: 172
• Q(SASA): 0.14
• 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
V/A	None	None	0.998	N	0.519	0.29	0.634485840324	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
V/A	0.4647	ambiguous	0.5043	ambiguous	-2.019	Highly Destabilizing	0.998	D	0.519	neutral	N	0.458751	None	None	N
V/C	0.7868	likely_pathogenic	0.7909	pathogenic	-1.828	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/D	0.9911	likely_pathogenic	0.9927	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.901	deleterious	N	0.50599322	None	None	N
V/E	0.9793	likely_pathogenic	0.9798	pathogenic	-1.862	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/F	0.6002	likely_pathogenic	0.5806	pathogenic	-1.354	Destabilizing	0.999	D	0.863	deleterious	N	0.485441742	None	None	N
V/G	0.7937	likely_pathogenic	0.8014	pathogenic	-2.507	Highly Destabilizing	1.0	D	0.877	deleterious	N	0.512609701	None	None	N
V/H	0.9867	likely_pathogenic	0.9867	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/I	0.0901	likely_benign	0.089	benign	-0.705	Destabilizing	0.767	D	0.311	neutral	N	0.435839641	None	None	N
V/K	0.9865	likely_pathogenic	0.9831	pathogenic	-1.744	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/L	0.4745	ambiguous	0.4509	ambiguous	-0.705	Destabilizing	0.981	D	0.533	neutral	N	0.495327875	None	None	N
V/M	0.4408	ambiguous	0.4079	ambiguous	-0.732	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
V/N	0.9606	likely_pathogenic	0.9653	pathogenic	-1.835	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/P	0.9898	likely_pathogenic	0.9919	pathogenic	-1.111	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/Q	0.9663	likely_pathogenic	0.9642	pathogenic	-1.79	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/R	0.9731	likely_pathogenic	0.9708	pathogenic	-1.436	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/S	0.8079	likely_pathogenic	0.8244	pathogenic	-2.538	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.6101	likely_pathogenic	0.6207	pathogenic	-2.246	Highly Destabilizing	0.998	D	0.638	neutral	None	None	None	None	N
V/W	0.9898	likely_pathogenic	0.9878	pathogenic	-1.678	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/Y	0.9482	likely_pathogenic	0.9442	pathogenic	-1.353	Destabilizing	1.0	D	0.871	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.