TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31538	94837;94838;94839	chr2:178546816;178546815;178546814	chr2:179411543;179411542;179411541
N2AB	29897	89914;89915;89916	chr2:178546816;178546815;178546814	chr2:179411543;179411542;179411541
N2A	28970	87133;87134;87135	chr2:178546816;178546815;178546814	chr2:179411543;179411542;179411541
N2B	22473	67642;67643;67644	chr2:178546816;178546815;178546814	chr2:179411543;179411542;179411541
Novex-1	22598	68017;68018;68019	chr2:178546816;178546815;178546814	chr2:179411543;179411542;179411541
Novex-2	22665	68218;68219;68220	chr2:178546816;178546815;178546814	chr2:179411543;179411542;179411541
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-118
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2272
• 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/I	rs1389165052	None	None	N	0.252	0.076	0.212008924253	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1389165052	None	None	N	0.252	0.076	0.212008924253	gnomAD-4.0.0	1.24083E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.48692E-07	0	1.60426E-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	0.8103	likely_pathogenic	0.7793	pathogenic	-1.628	Destabilizing	0.296	N	0.662	neutral	N	0.499832295	None	None	I
V/C	0.954	likely_pathogenic	0.9503	pathogenic	-1.109	Destabilizing	0.991	D	0.767	deleterious	None	None	None	None	I
V/D	0.984	likely_pathogenic	0.9872	pathogenic	-1.589	Destabilizing	0.879	D	0.849	deleterious	N	0.481132155	None	None	I
V/E	0.962	likely_pathogenic	0.9659	pathogenic	-1.576	Destabilizing	0.906	D	0.823	deleterious	None	None	None	None	I
V/F	0.8098	likely_pathogenic	0.8384	pathogenic	-1.25	Destabilizing	0.782	D	0.831	deleterious	N	0.489410587	None	None	I
V/G	0.8933	likely_pathogenic	0.8986	pathogenic	-1.968	Destabilizing	0.879	D	0.833	deleterious	N	0.507594202	None	None	I
V/H	0.9877	likely_pathogenic	0.9896	pathogenic	-1.493	Destabilizing	0.991	D	0.819	deleterious	None	None	None	None	I
V/I	0.0706	likely_benign	0.0708	benign	-0.785	Destabilizing	None	N	0.252	neutral	N	0.365325472	None	None	I
V/K	0.9779	likely_pathogenic	0.9782	pathogenic	-1.419	Destabilizing	0.906	D	0.823	deleterious	None	None	None	None	I
V/L	0.3627	ambiguous	0.3674	ambiguous	-0.785	Destabilizing	0.031	N	0.497	neutral	N	0.454584826	None	None	I
V/M	0.5207	ambiguous	0.5214	ambiguous	-0.552	Destabilizing	0.826	D	0.691	prob.neutral	None	None	None	None	I
V/N	0.9137	likely_pathogenic	0.9291	pathogenic	-1.248	Destabilizing	0.967	D	0.85	deleterious	None	None	None	None	I
V/P	0.8504	likely_pathogenic	0.8242	pathogenic	-1.031	Destabilizing	0.967	D	0.805	deleterious	None	None	None	None	I
V/Q	0.9673	likely_pathogenic	0.9681	pathogenic	-1.41	Destabilizing	0.967	D	0.802	deleterious	None	None	None	None	I
V/R	0.9647	likely_pathogenic	0.9653	pathogenic	-0.862	Destabilizing	0.906	D	0.851	deleterious	None	None	None	None	I
V/S	0.9151	likely_pathogenic	0.911	pathogenic	-1.778	Destabilizing	0.906	D	0.809	deleterious	None	None	None	None	I
V/T	0.749	likely_pathogenic	0.7287	pathogenic	-1.654	Destabilizing	0.575	D	0.729	prob.delet.	None	None	None	None	I
V/W	0.9906	likely_pathogenic	0.9927	pathogenic	-1.468	Destabilizing	0.991	D	0.81	deleterious	None	None	None	None	I
V/Y	0.9705	likely_pathogenic	0.9739	pathogenic	-1.182	Destabilizing	0.906	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.