TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20389	61390;61391;61392	chr2:178590560;178590559;178590558	chr2:179455287;179455286;179455285
N2AB	18748	56467;56468;56469	chr2:178590560;178590559;178590558	chr2:179455287;179455286;179455285
N2A	17821	53686;53687;53688	chr2:178590560;178590559;178590558	chr2:179455287;179455286;179455285
N2B	11324	34195;34196;34197	chr2:178590560;178590559;178590558	chr2:179455287;179455286;179455285
Novex-1	11449	34570;34571;34572	chr2:178590560;178590559;178590558	chr2:179455287;179455286;179455285
Novex-2	11516	34771;34772;34773	chr2:178590560;178590559;178590558	chr2:179455287;179455286;179455285
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-36
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1893
• 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
D/H	rs1410268896	None	0.997	N	0.771	0.352	0.354610295913	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/H	rs1410268896	None	0.997	N	0.771	0.352	0.354610295913	gnomAD-4.0.0	6.57748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47128E-05	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
D/A	0.7477	likely_pathogenic	0.7118	pathogenic	-0.344	Destabilizing	0.865	D	0.621	neutral	N	0.472495796	None	None	N
D/C	0.941	likely_pathogenic	0.9374	pathogenic	-0.296	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
D/E	0.5469	ambiguous	0.5496	ambiguous	-0.894	Destabilizing	0.039	N	0.289	neutral	N	0.482307358	None	None	N
D/F	0.9084	likely_pathogenic	0.8978	pathogenic	-0.423	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
D/G	0.8769	likely_pathogenic	0.8374	pathogenic	-0.688	Destabilizing	0.928	D	0.603	neutral	N	0.467734707	None	None	N
D/H	0.8174	likely_pathogenic	0.7713	pathogenic	-0.931	Destabilizing	0.997	D	0.771	deleterious	N	0.512803623	None	None	N
D/I	0.8732	likely_pathogenic	0.8387	pathogenic	0.556	Stabilizing	0.992	D	0.836	deleterious	None	None	None	None	N
D/K	0.9529	likely_pathogenic	0.9331	pathogenic	-0.685	Destabilizing	0.968	D	0.677	prob.neutral	None	None	None	None	N
D/L	0.8627	likely_pathogenic	0.838	pathogenic	0.556	Stabilizing	0.983	D	0.791	deleterious	None	None	None	None	N
D/M	0.9419	likely_pathogenic	0.9341	pathogenic	0.998	Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
D/N	0.4735	ambiguous	0.4279	ambiguous	-0.909	Destabilizing	0.978	D	0.657	neutral	N	0.48074992	None	None	N
D/P	0.996	likely_pathogenic	0.9954	pathogenic	0.282	Stabilizing	0.992	D	0.744	deleterious	None	None	None	None	N
D/Q	0.9022	likely_pathogenic	0.8811	pathogenic	-0.747	Destabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	N
D/R	0.9603	likely_pathogenic	0.9424	pathogenic	-0.725	Destabilizing	0.983	D	0.757	deleterious	None	None	None	None	N
D/S	0.5244	ambiguous	0.4708	ambiguous	-1.242	Destabilizing	0.895	D	0.51	neutral	None	None	None	None	N
D/T	0.7235	likely_pathogenic	0.6543	pathogenic	-0.96	Destabilizing	0.983	D	0.701	prob.neutral	None	None	None	None	N
D/V	0.7274	likely_pathogenic	0.6788	pathogenic	0.282	Stabilizing	0.978	D	0.778	deleterious	N	0.462662804	None	None	N
D/W	0.9828	likely_pathogenic	0.9791	pathogenic	-0.53	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
D/Y	0.6802	likely_pathogenic	0.621	pathogenic	-0.263	Destabilizing	0.999	D	0.831	deleterious	D	0.522481899	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.