TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24450	73573;73574;73575	chr2:178572784;178572783;178572782	chr2:179437511;179437510;179437509
N2AB	22809	68650;68651;68652	chr2:178572784;178572783;178572782	chr2:179437511;179437510;179437509
N2A	21882	65869;65870;65871	chr2:178572784;178572783;178572782	chr2:179437511;179437510;179437509
N2B	15385	46378;46379;46380	chr2:178572784;178572783;178572782	chr2:179437511;179437510;179437509
Novex-1	15510	46753;46754;46755	chr2:178572784;178572783;178572782	chr2:179437511;179437510;179437509
Novex-2	15577	46954;46955;46956	chr2:178572784;178572783;178572782	chr2:179437511;179437510;179437509
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: Ig-132
• Domain position: 20
• Structural Position: 33
• Q(SASA): 0.1602
• 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/A	None	None	0.025	N	0.408	0.197	0.342631996419	gnomAD-4.0.0	6.84326E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9959E-07	0	0
V/F	rs771025206	-0.963	0.983	N	0.771	0.524	0.771652491224	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/F	rs771025206	-0.963	0.983	N	0.771	0.524	0.771652491224	gnomAD-4.0.0	2.7374E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59841E-06	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	0.8051	likely_pathogenic	0.7925	pathogenic	-1.523	Destabilizing	0.025	N	0.408	neutral	N	0.457805984	None	None	I
V/C	0.9298	likely_pathogenic	0.9288	pathogenic	-0.948	Destabilizing	0.997	D	0.774	deleterious	None	None	None	None	I
V/D	0.9987	likely_pathogenic	0.9985	pathogenic	-1.735	Destabilizing	0.983	D	0.863	deleterious	N	0.497918239	None	None	I
V/E	0.9954	likely_pathogenic	0.9947	pathogenic	-1.544	Destabilizing	0.975	D	0.826	deleterious	None	None	None	None	I
V/F	0.8208	likely_pathogenic	0.818	pathogenic	-0.912	Destabilizing	0.983	D	0.771	deleterious	N	0.49766475	None	None	I
V/G	0.9548	likely_pathogenic	0.9503	pathogenic	-1.985	Destabilizing	0.935	D	0.803	deleterious	N	0.471166704	None	None	I
V/H	0.9972	likely_pathogenic	0.9968	pathogenic	-1.461	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	I
V/I	0.1013	likely_benign	0.1052	benign	-0.263	Destabilizing	0.773	D	0.589	neutral	N	0.473044796	None	None	I
V/K	0.9963	likely_pathogenic	0.9959	pathogenic	-1.181	Destabilizing	0.975	D	0.829	deleterious	None	None	None	None	I
V/L	0.656	likely_pathogenic	0.6674	pathogenic	-0.263	Destabilizing	0.63	D	0.686	prob.neutral	N	0.484876413	None	None	I
V/M	0.7678	likely_pathogenic	0.7648	pathogenic	-0.279	Destabilizing	0.996	D	0.724	prob.delet.	None	None	None	None	I
V/N	0.9944	likely_pathogenic	0.9933	pathogenic	-1.504	Destabilizing	0.987	D	0.861	deleterious	None	None	None	None	I
V/P	0.9952	likely_pathogenic	0.9947	pathogenic	-0.655	Destabilizing	0.987	D	0.841	deleterious	None	None	None	None	I
V/Q	0.9908	likely_pathogenic	0.9893	pathogenic	-1.374	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	I
V/R	0.9908	likely_pathogenic	0.9896	pathogenic	-1.026	Destabilizing	0.987	D	0.85	deleterious	None	None	None	None	I
V/S	0.9415	likely_pathogenic	0.9309	pathogenic	-2.088	Highly Destabilizing	0.95	D	0.791	deleterious	None	None	None	None	I
V/T	0.9094	likely_pathogenic	0.9011	pathogenic	-1.749	Destabilizing	0.916	D	0.695	prob.neutral	None	None	None	None	I
V/W	0.9979	likely_pathogenic	0.9978	pathogenic	-1.295	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	I
V/Y	0.9897	likely_pathogenic	0.989	pathogenic	-0.866	Destabilizing	0.996	D	0.759	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.