TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26217	78874;78875;78876	chr2:178567483;178567482;178567481	chr2:179432210;179432209;179432208
N2AB	24576	73951;73952;73953	chr2:178567483;178567482;178567481	chr2:179432210;179432209;179432208
N2A	23649	71170;71171;71172	chr2:178567483;178567482;178567481	chr2:179432210;179432209;179432208
N2B	17152	51679;51680;51681	chr2:178567483;178567482;178567481	chr2:179432210;179432209;179432208
Novex-1	17277	52054;52055;52056	chr2:178567483;178567482;178567481	chr2:179432210;179432209;179432208
Novex-2	17344	52255;52256;52257	chr2:178567483;178567482;178567481	chr2:179432210;179432209;179432208
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-137
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.0915
• 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	rs748869015	-2.4	0.998	N	0.659	0.64	0.633262315121	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
V/A	rs748869015	-2.4	0.998	N	0.659	0.64	0.633262315121	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43497E-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	0.8712	likely_pathogenic	0.8418	pathogenic	-1.952	Destabilizing	0.998	D	0.659	neutral	N	0.504593225	None	None	N
V/C	0.9312	likely_pathogenic	0.9135	pathogenic	-1.435	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/D	0.9967	likely_pathogenic	0.997	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.618732653	None	None	N
V/E	0.9912	likely_pathogenic	0.9914	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/F	0.6068	likely_pathogenic	0.5915	pathogenic	-1.264	Destabilizing	0.999	D	0.837	deleterious	D	0.546186558	None	None	N
V/G	0.9373	likely_pathogenic	0.9331	pathogenic	-2.409	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.602713292	None	None	N
V/H	0.9938	likely_pathogenic	0.9932	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/I	0.0789	likely_benign	0.0758	benign	-0.725	Destabilizing	0.767	D	0.297	neutral	N	0.46876571	None	None	N
V/K	0.991	likely_pathogenic	0.991	pathogenic	-1.63	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
V/L	0.5803	likely_pathogenic	0.5322	ambiguous	-0.725	Destabilizing	0.981	D	0.649	neutral	D	0.537980433	None	None	N
V/M	0.5547	ambiguous	0.5241	ambiguous	-0.635	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/N	0.9862	likely_pathogenic	0.9852	pathogenic	-1.659	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/P	0.9954	likely_pathogenic	0.9946	pathogenic	-1.103	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/Q	0.9883	likely_pathogenic	0.9879	pathogenic	-1.668	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/R	0.9823	likely_pathogenic	0.9827	pathogenic	-1.283	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/S	0.9503	likely_pathogenic	0.9437	pathogenic	-2.251	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/T	0.841	likely_pathogenic	0.8156	pathogenic	-2.006	Highly Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
V/W	0.9906	likely_pathogenic	0.9892	pathogenic	-1.67	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9501	likely_pathogenic	0.9491	pathogenic	-1.335	Destabilizing	1.0	D	0.841	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.