TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25707	77344;77345;77346	chr2:178569013;178569012;178569011	chr2:179433740;179433739;179433738
N2AB	24066	72421;72422;72423	chr2:178569013;178569012;178569011	chr2:179433740;179433739;179433738
N2A	23139	69640;69641;69642	chr2:178569013;178569012;178569011	chr2:179433740;179433739;179433738
N2B	16642	50149;50150;50151	chr2:178569013;178569012;178569011	chr2:179433740;179433739;179433738
Novex-1	16767	50524;50525;50526	chr2:178569013;178569012;178569011	chr2:179433740;179433739;179433738
Novex-2	16834	50725;50726;50727	chr2:178569013;178569012;178569011	chr2:179433740;179433739;179433738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-75
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.437
• 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
V/L	None	None	0.618	N	0.38	0.208	0.29132392195	gnomAD-4.0.0	6.84395E-07	None	None	None	None	I	None	2.99061E-05	0	None	0	0	None	0	0	0	0	0
V/M	rs1192473018	-0.596	0.825	N	0.323	0.293	0.364730456448	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/M	rs1192473018	-0.596	0.825	N	0.323	0.293	0.364730456448	gnomAD-4.0.0	6.84395E-07	None	None	None	None	I	None	2.99061E-05	0	None	0	0	None	0	0	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	0.428	ambiguous	0.3552	ambiguous	-1.502	Destabilizing	0.958	D	0.53	neutral	N	0.509958106	None	None	I
V/C	0.9158	likely_pathogenic	0.8945	pathogenic	-1.482	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
V/D	0.9774	likely_pathogenic	0.9669	pathogenic	-0.648	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	I
V/E	0.9363	likely_pathogenic	0.9199	pathogenic	-0.585	Destabilizing	0.994	D	0.799	deleterious	N	0.521360499	None	None	I
V/F	0.5781	likely_pathogenic	0.511	ambiguous	-1.065	Destabilizing	0.991	D	0.8	deleterious	None	None	None	None	I
V/G	0.7711	likely_pathogenic	0.7173	pathogenic	-1.875	Destabilizing	0.994	D	0.787	deleterious	N	0.520346541	None	None	I
V/H	0.975	likely_pathogenic	0.9663	pathogenic	-1.268	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
V/I	0.0984	likely_benign	0.0909	benign	-0.559	Destabilizing	0.862	D	0.577	neutral	None	None	None	None	I
V/K	0.9369	likely_pathogenic	0.9234	pathogenic	-1.154	Destabilizing	0.991	D	0.781	deleterious	None	None	None	None	I
V/L	0.4146	ambiguous	0.3415	ambiguous	-0.559	Destabilizing	0.618	D	0.38	neutral	N	0.455569048	None	None	I
V/M	0.3221	likely_benign	0.2635	benign	-0.683	Destabilizing	0.825	D	0.323	neutral	N	0.484138031	None	None	I
V/N	0.9423	likely_pathogenic	0.9152	pathogenic	-1.132	Destabilizing	0.995	D	0.851	deleterious	None	None	None	None	I
V/P	0.8557	likely_pathogenic	0.8176	pathogenic	-0.839	Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	I
V/Q	0.9243	likely_pathogenic	0.9036	pathogenic	-1.135	Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	I
V/R	0.9104	likely_pathogenic	0.8948	pathogenic	-0.807	Destabilizing	0.995	D	0.849	deleterious	None	None	None	None	I
V/S	0.7946	likely_pathogenic	0.7316	pathogenic	-1.848	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	I
V/T	0.5208	ambiguous	0.4687	ambiguous	-1.63	Destabilizing	0.968	D	0.619	neutral	None	None	None	None	I
V/W	0.9703	likely_pathogenic	0.9613	pathogenic	-1.195	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/Y	0.9357	likely_pathogenic	0.9161	pathogenic	-0.904	Destabilizing	0.995	D	0.817	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.