TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18662	56209;56210;56211	chr2:178600920;178600919;178600918	chr2:179465647;179465646;179465645
N2AB	17021	51286;51287;51288	chr2:178600920;178600919;178600918	chr2:179465647;179465646;179465645
N2A	16094	48505;48506;48507	chr2:178600920;178600919;178600918	chr2:179465647;179465646;179465645
N2B	9597	29014;29015;29016	chr2:178600920;178600919;178600918	chr2:179465647;179465646;179465645
Novex-1	9722	29389;29390;29391	chr2:178600920;178600919;178600918	chr2:179465647;179465646;179465645
Novex-2	9789	29590;29591;29592	chr2:178600920;178600919;178600918	chr2:179465647;179465646;179465645
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: Fn3-23
• Domain position: 84
• Structural Position: 111
• Q(SASA): 0.087
• 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/L	rs746969341	-0.548	0.987	N	0.52	0.253	0.52730433808	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
V/L	rs746969341	-0.548	0.987	N	0.52	0.253	0.52730433808	gnomAD-4.0.0	2.56482E-06	None	None	None	None	N	None	0	1.6963E-05	None	0	0	None	0	0	0	0	2.84738E-05

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	0.4306	ambiguous	0.4288	ambiguous	-1.997	Destabilizing	0.994	D	0.517	neutral	N	0.476936009	None	None	N
V/C	0.7935	likely_pathogenic	0.7647	pathogenic	-1.7	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/D	0.8989	likely_pathogenic	0.9239	pathogenic	-2.878	Highly Destabilizing	0.998	D	0.84	deleterious	N	0.508589069	None	None	N
V/E	0.5173	ambiguous	0.5944	pathogenic	-2.737	Highly Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
V/F	0.3261	likely_benign	0.3067	benign	-1.286	Destabilizing	0.998	D	0.758	deleterious	N	0.49053404	None	None	N
V/G	0.6449	likely_pathogenic	0.6592	pathogenic	-2.435	Highly Destabilizing	0.998	D	0.795	deleterious	N	0.490231325	None	None	N
V/H	0.8204	likely_pathogenic	0.8113	pathogenic	-2.112	Highly Destabilizing	0.46	N	0.609	neutral	None	None	None	None	N
V/I	0.1089	likely_benign	0.1023	benign	-0.807	Destabilizing	0.996	D	0.518	neutral	N	0.510329039	None	None	N
V/K	0.5357	ambiguous	0.588	pathogenic	-1.604	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
V/L	0.4771	ambiguous	0.4692	ambiguous	-0.807	Destabilizing	0.987	D	0.52	neutral	N	0.518985808	None	None	N
V/M	0.2622	likely_benign	0.2507	benign	-0.891	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
V/N	0.7876	likely_pathogenic	0.7958	pathogenic	-1.83	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
V/P	0.9911	likely_pathogenic	0.9931	pathogenic	-1.177	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/Q	0.4577	ambiguous	0.4841	ambiguous	-1.814	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/R	0.4778	ambiguous	0.5355	ambiguous	-1.288	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
V/S	0.5926	likely_pathogenic	0.6048	pathogenic	-2.346	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
V/T	0.4445	ambiguous	0.4577	ambiguous	-2.088	Highly Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
V/W	0.9325	likely_pathogenic	0.9268	pathogenic	-1.762	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/Y	0.7546	likely_pathogenic	0.7473	pathogenic	-1.423	Destabilizing	0.998	D	0.754	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.