TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17805	53638;53639;53640	chr2:178607189;178607188;178607187	chr2:179471916;179471915;179471914
N2AB	16164	48715;48716;48717	chr2:178607189;178607188;178607187	chr2:179471916;179471915;179471914
N2A	15237	45934;45935;45936	chr2:178607189;178607188;178607187	chr2:179471916;179471915;179471914
N2B	8740	26443;26444;26445	chr2:178607189;178607188;178607187	chr2:179471916;179471915;179471914
Novex-1	8865	26818;26819;26820	chr2:178607189;178607188;178607187	chr2:179471916;179471915;179471914
Novex-2	8932	27019;27020;27021	chr2:178607189;178607188;178607187	chr2:179471916;179471915;179471914
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: Fn3-17
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2499
• 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/Y	rs1051218836	-0.056	0.999	N	0.813	0.427	0.75224819921	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/Y	rs1051218836	-0.056	0.999	N	0.813	0.427	0.75224819921	gnomAD-4.0.0	2.05351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73671E-04	0	0	3.31554E-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
D/A	0.9651	likely_pathogenic	0.9569	pathogenic	-0.73	Destabilizing	0.865	D	0.626	neutral	N	0.471595821	None	None	N
D/C	0.9894	likely_pathogenic	0.9872	pathogenic	-0.475	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
D/E	0.8149	likely_pathogenic	0.7968	pathogenic	-0.794	Destabilizing	0.039	N	0.229	neutral	N	0.457640987	None	None	N
D/F	0.9933	likely_pathogenic	0.9938	pathogenic	-0.317	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
D/G	0.9655	likely_pathogenic	0.9606	pathogenic	-1.089	Destabilizing	0.928	D	0.615	neutral	N	0.482649411	None	None	N
D/H	0.9804	likely_pathogenic	0.9789	pathogenic	-0.735	Destabilizing	0.997	D	0.778	deleterious	N	0.496639063	None	None	N
D/I	0.9897	likely_pathogenic	0.9899	pathogenic	0.228	Stabilizing	0.992	D	0.828	deleterious	None	None	None	None	N
D/K	0.9923	likely_pathogenic	0.9921	pathogenic	-0.95	Destabilizing	0.968	D	0.671	neutral	None	None	None	None	N
D/L	0.9808	likely_pathogenic	0.9811	pathogenic	0.228	Stabilizing	0.983	D	0.81	deleterious	None	None	None	None	N
D/M	0.9935	likely_pathogenic	0.9936	pathogenic	0.718	Stabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
D/N	0.8656	likely_pathogenic	0.8346	pathogenic	-1.25	Destabilizing	0.978	D	0.671	neutral	N	0.484268799	None	None	N
D/P	0.9948	likely_pathogenic	0.9929	pathogenic	-0.067	Destabilizing	0.992	D	0.787	deleterious	None	None	None	None	N
D/Q	0.9868	likely_pathogenic	0.9864	pathogenic	-1.095	Destabilizing	0.968	D	0.761	deleterious	None	None	None	None	N
D/R	0.9925	likely_pathogenic	0.9928	pathogenic	-0.726	Destabilizing	0.983	D	0.799	deleterious	None	None	None	None	N
D/S	0.9556	likely_pathogenic	0.9447	pathogenic	-1.559	Destabilizing	0.895	D	0.568	neutral	None	None	None	None	N
D/T	0.9816	likely_pathogenic	0.9789	pathogenic	-1.276	Destabilizing	0.983	D	0.677	prob.neutral	None	None	None	None	N
D/V	0.9691	likely_pathogenic	0.9671	pathogenic	-0.067	Destabilizing	0.978	D	0.808	deleterious	N	0.491866123	None	None	N
D/W	0.998	likely_pathogenic	0.9982	pathogenic	-0.181	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
D/Y	0.9603	likely_pathogenic	0.9585	pathogenic	-0.133	Destabilizing	0.999	D	0.813	deleterious	N	0.515757276	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.