TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22285	67078;67079;67080	chr2:178580526;178580525;178580524	chr2:179445253;179445252;179445251
N2AB	20644	62155;62156;62157	chr2:178580526;178580525;178580524	chr2:179445253;179445252;179445251
N2A	19717	59374;59375;59376	chr2:178580526;178580525;178580524	chr2:179445253;179445252;179445251
N2B	13220	39883;39884;39885	chr2:178580526;178580525;178580524	chr2:179445253;179445252;179445251
Novex-1	13345	40258;40259;40260	chr2:178580526;178580525;178580524	chr2:179445253;179445252;179445251
Novex-2	13412	40459;40460;40461	chr2:178580526;178580525;178580524	chr2:179445253;179445252;179445251
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-126
• Domain position: 21
• Structural Position: 35
• Q(SASA): 0.3422
• 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	None	None	0.248	N	0.303	0.141	0.414798848334	gnomAD-4.0.0	6.84633E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99815E-07	0	0
V/L	rs754121833	-0.467	0.031	D	0.27	0.244	0.45746916685	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
V/L	rs754121833	-0.467	0.031	D	0.27	0.244	0.45746916685	gnomAD-4.0.0	6.84633E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99815E-07	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	0.7835	likely_pathogenic	0.7698	pathogenic	-1.51	Destabilizing	0.954	D	0.599	neutral	N	0.502168995	None	None	I
V/C	0.8792	likely_pathogenic	0.8712	pathogenic	-1.01	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
V/D	0.9967	likely_pathogenic	0.9954	pathogenic	-1.331	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	I
V/E	0.9885	likely_pathogenic	0.9856	pathogenic	-1.287	Destabilizing	0.998	D	0.746	deleterious	D	0.588319083	None	None	I
V/F	0.6034	likely_pathogenic	0.5414	ambiguous	-1.039	Destabilizing	0.991	D	0.718	prob.delet.	None	None	None	None	I
V/G	0.9093	likely_pathogenic	0.8811	pathogenic	-1.877	Destabilizing	0.998	D	0.757	deleterious	D	0.562780972	None	None	I
V/H	0.9899	likely_pathogenic	0.9857	pathogenic	-1.419	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
V/I	0.1061	likely_benign	0.106	benign	-0.585	Destabilizing	0.248	N	0.303	neutral	N	0.475499682	None	None	I
V/K	0.9876	likely_pathogenic	0.9837	pathogenic	-1.322	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
V/L	0.5053	ambiguous	0.4834	ambiguous	-0.585	Destabilizing	0.031	N	0.27	neutral	D	0.568055218	None	None	I
V/M	0.5461	ambiguous	0.5215	ambiguous	-0.477	Destabilizing	0.991	D	0.659	neutral	None	None	None	None	I
V/N	0.9816	likely_pathogenic	0.9749	pathogenic	-1.157	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	I
V/P	0.9853	likely_pathogenic	0.9809	pathogenic	-0.859	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
V/Q	0.9759	likely_pathogenic	0.9699	pathogenic	-1.248	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	I
V/R	0.9754	likely_pathogenic	0.9678	pathogenic	-0.869	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
V/S	0.923	likely_pathogenic	0.9097	pathogenic	-1.708	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
V/T	0.8269	likely_pathogenic	0.8109	pathogenic	-1.541	Destabilizing	0.985	D	0.621	neutral	None	None	None	None	I
V/W	0.9909	likely_pathogenic	0.9877	pathogenic	-1.28	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
V/Y	0.9516	likely_pathogenic	0.939	pathogenic	-0.976	Destabilizing	0.999	D	0.715	prob.delet.	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.