TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21603	65032;65033;65034	chr2:178584834;178584833;178584832	chr2:179449561;179449560;179449559
N2AB	19962	60109;60110;60111	chr2:178584834;178584833;178584832	chr2:179449561;179449560;179449559
N2A	19035	57328;57329;57330	chr2:178584834;178584833;178584832	chr2:179449561;179449560;179449559
N2B	12538	37837;37838;37839	chr2:178584834;178584833;178584832	chr2:179449561;179449560;179449559
Novex-1	12663	38212;38213;38214	chr2:178584834;178584833;178584832	chr2:179449561;179449560;179449559
Novex-2	12730	38413;38414;38415	chr2:178584834;178584833;178584832	chr2:179449561;179449560;179449559
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-44
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.4632
• 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
S/C	None	None	0.999	N	0.449	0.392	0.490631539035	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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
S/A	0.0835	likely_benign	0.0847	benign	-0.231	Destabilizing	0.702	D	0.341	neutral	None	None	None	None	N
S/C	0.1474	likely_benign	0.1442	benign	-0.318	Destabilizing	0.999	D	0.449	neutral	N	0.492893308	None	None	N
S/D	0.3621	ambiguous	0.493	ambiguous	-0.014	Destabilizing	0.959	D	0.253	neutral	None	None	None	None	N
S/E	0.3996	ambiguous	0.5301	ambiguous	-0.126	Destabilizing	0.959	D	0.25	neutral	None	None	None	None	N
S/F	0.2365	likely_benign	0.2646	benign	-0.941	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
S/G	0.1046	likely_benign	0.1103	benign	-0.287	Destabilizing	0.026	N	0.283	neutral	N	0.433590691	None	None	N
S/H	0.3025	likely_benign	0.3923	ambiguous	-0.671	Destabilizing	0.999	D	0.406	neutral	None	None	None	None	N
S/I	0.1898	likely_benign	0.2122	benign	-0.217	Destabilizing	0.968	D	0.548	neutral	N	0.477498078	None	None	N
S/K	0.5085	ambiguous	0.6742	pathogenic	-0.422	Destabilizing	0.919	D	0.25	neutral	None	None	None	None	N
S/L	0.1067	likely_benign	0.1073	benign	-0.217	Destabilizing	0.919	D	0.404	neutral	None	None	None	None	N
S/M	0.2151	likely_benign	0.2177	benign	-0.056	Destabilizing	0.999	D	0.412	neutral	None	None	None	None	N
S/N	0.15	likely_benign	0.1703	benign	-0.162	Destabilizing	0.896	D	0.316	neutral	N	0.468241982	None	None	N
S/P	0.4065	ambiguous	0.4422	ambiguous	-0.197	Destabilizing	0.996	D	0.37	neutral	None	None	None	None	N
S/Q	0.3763	ambiguous	0.4741	ambiguous	-0.425	Destabilizing	0.996	D	0.293	neutral	None	None	None	None	N
S/R	0.4375	ambiguous	0.609	pathogenic	-0.15	Destabilizing	0.984	D	0.366	neutral	N	0.451544521	None	None	N
S/T	0.0778	likely_benign	0.0793	benign	-0.279	Destabilizing	0.103	N	0.283	neutral	N	0.449832367	None	None	N
S/V	0.1912	likely_benign	0.199	benign	-0.197	Destabilizing	0.976	D	0.447	neutral	None	None	None	None	N
S/W	0.3698	ambiguous	0.4372	ambiguous	-0.992	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
S/Y	0.2257	likely_benign	0.2684	benign	-0.693	Destabilizing	0.996	D	0.559	neutral	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.