TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20327	61204;61205;61206	chr2:178590746;178590745;178590744	chr2:179455473;179455472;179455471
N2AB	18686	56281;56282;56283	chr2:178590746;178590745;178590744	chr2:179455473;179455472;179455471
N2A	17759	53500;53501;53502	chr2:178590746;178590745;178590744	chr2:179455473;179455472;179455471
N2B	11262	34009;34010;34011	chr2:178590746;178590745;178590744	chr2:179455473;179455472;179455471
Novex-1	11387	34384;34385;34386	chr2:178590746;178590745;178590744	chr2:179455473;179455472;179455471
Novex-2	11454	34585;34586;34587	chr2:178590746;178590745;178590744	chr2:179455473;179455472;179455471
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-35
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.658
• 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/E	None	None	0.619	N	0.277	0.057	0.212008924253	gnomAD-4.0.0	6.85362E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00705E-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
D/A	0.2183	likely_benign	0.1799	benign	0.208	Stabilizing	0.998	D	0.685	prob.neutral	N	0.498951679	None	None	N
D/C	0.6778	likely_pathogenic	0.6104	pathogenic	-0.192	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/E	0.1722	likely_benign	0.1431	benign	-0.489	Destabilizing	0.619	D	0.277	neutral	N	0.463145594	None	None	N
D/F	0.6863	likely_pathogenic	0.6501	pathogenic	0.721	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/G	0.1858	likely_benign	0.1463	benign	-0.087	Destabilizing	0.996	D	0.727	prob.delet.	N	0.511688902	None	None	N
D/H	0.3996	ambiguous	0.3401	ambiguous	1.035	Stabilizing	1.0	D	0.737	prob.delet.	N	0.477129229	None	None	N
D/I	0.5793	likely_pathogenic	0.5034	ambiguous	0.966	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
D/K	0.5551	ambiguous	0.4454	ambiguous	0.308	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
D/L	0.5055	ambiguous	0.4248	ambiguous	0.966	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
D/M	0.6757	likely_pathogenic	0.6163	pathogenic	0.751	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
D/N	0.1285	likely_benign	0.1146	benign	-0.394	Destabilizing	0.999	D	0.661	neutral	N	0.519094877	None	None	N
D/P	0.846	likely_pathogenic	0.8005	pathogenic	0.738	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
D/Q	0.4286	ambiguous	0.3506	ambiguous	-0.238	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
D/R	0.5901	likely_pathogenic	0.5029	ambiguous	0.673	Stabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
D/S	0.1381	likely_benign	0.124	benign	-0.52	Destabilizing	0.994	D	0.639	neutral	None	None	None	None	N
D/T	0.3123	likely_benign	0.2572	benign	-0.248	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
D/V	0.3701	ambiguous	0.3033	benign	0.738	Stabilizing	0.999	D	0.783	deleterious	N	0.50970739	None	None	N
D/W	0.9308	likely_pathogenic	0.9106	pathogenic	0.846	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/Y	0.3538	ambiguous	0.3052	benign	0.996	Stabilizing	1.0	D	0.768	deleterious	N	0.479913933	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.