TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25571	76936;76937;76938	chr2:178569421;178569420;178569419	chr2:179434148;179434147;179434146
N2AB	23930	72013;72014;72015	chr2:178569421;178569420;178569419	chr2:179434148;179434147;179434146
N2A	23003	69232;69233;69234	chr2:178569421;178569420;178569419	chr2:179434148;179434147;179434146
N2B	16506	49741;49742;49743	chr2:178569421;178569420;178569419	chr2:179434148;179434147;179434146
Novex-1	16631	50116;50117;50118	chr2:178569421;178569420;178569419	chr2:179434148;179434147;179434146
Novex-2	16698	50317;50318;50319	chr2:178569421;178569420;178569419	chr2:179434148;179434147;179434146
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-135
• Domain position: 58
• Structural Position: 144
• Q(SASA): 0.0939
• 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/I	rs760782774	-0.836	0.997	N	0.492	0.342	0.721245998615	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	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	0.4654	ambiguous	0.4765	ambiguous	-1.701	Destabilizing	0.999	D	0.502	neutral	N	0.516436653	None	None	N
V/C	0.8207	likely_pathogenic	0.8328	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
V/D	0.9894	likely_pathogenic	0.9896	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.735	prob.delet.	D	0.554526449	None	None	N
V/E	0.9779	likely_pathogenic	0.9791	pathogenic	-2.597	Highly Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
V/F	0.9077	likely_pathogenic	0.9158	pathogenic	-1.485	Destabilizing	1.0	D	0.741	deleterious	D	0.55376598	None	None	N
V/G	0.7631	likely_pathogenic	0.7809	pathogenic	-2.016	Highly Destabilizing	1.0	D	0.711	prob.delet.	D	0.542916654	None	None	N
V/H	0.9935	likely_pathogenic	0.9937	pathogenic	-1.429	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/I	0.152	likely_benign	0.1472	benign	-0.905	Destabilizing	0.997	D	0.492	neutral	N	0.495344476	None	None	N
V/K	0.9864	likely_pathogenic	0.9869	pathogenic	-1.499	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/L	0.704	likely_pathogenic	0.7116	pathogenic	-0.905	Destabilizing	0.997	D	0.519	neutral	D	0.53643071	None	None	N
V/M	0.5567	ambiguous	0.5725	pathogenic	-1.082	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/N	0.9463	likely_pathogenic	0.9452	pathogenic	-1.652	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/P	0.968	likely_pathogenic	0.9696	pathogenic	-1.141	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/Q	0.9717	likely_pathogenic	0.9728	pathogenic	-1.861	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
V/R	0.9793	likely_pathogenic	0.9801	pathogenic	-0.988	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/S	0.6882	likely_pathogenic	0.6879	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/T	0.5218	ambiguous	0.4977	ambiguous	-1.983	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
V/W	0.9982	likely_pathogenic	0.9985	pathogenic	-1.68	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
V/Y	0.9907	likely_pathogenic	0.9919	pathogenic	-1.339	Destabilizing	1.0	D	0.743	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.