TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17770	53533;53534;53535	chr2:178607294;178607293;178607292	chr2:179472021;179472020;179472019
N2AB	16129	48610;48611;48612	chr2:178607294;178607293;178607292	chr2:179472021;179472020;179472019
N2A	15202	45829;45830;45831	chr2:178607294;178607293;178607292	chr2:179472021;179472020;179472019
N2B	8705	26338;26339;26340	chr2:178607294;178607293;178607292	chr2:179472021;179472020;179472019
Novex-1	8830	26713;26714;26715	chr2:178607294;178607293;178607292	chr2:179472021;179472020;179472019
Novex-2	8897	26914;26915;26916	chr2:178607294;178607293;178607292	chr2:179472021;179472020;179472019
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: Fn3-17
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.084
• 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	1.0	N	0.627	0.284	0.283761946502	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.5464	ambiguous	0.495	ambiguous	-0.247	Destabilizing	1.0	D	0.773	deleterious	N	0.515361139	None	None	N
D/C	0.8837	likely_pathogenic	0.8761	pathogenic	-0.121	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/E	0.4267	ambiguous	0.3885	ambiguous	-0.332	Destabilizing	1.0	D	0.627	neutral	N	0.48923333	None	None	N
D/F	0.8885	likely_pathogenic	0.8562	pathogenic	-0.048	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
D/G	0.4261	ambiguous	0.4171	ambiguous	-0.464	Destabilizing	1.0	D	0.754	deleterious	N	0.50808845	None	None	N
D/H	0.7151	likely_pathogenic	0.6611	pathogenic	0.188	Stabilizing	1.0	D	0.801	deleterious	N	0.479304822	None	None	N
D/I	0.9082	likely_pathogenic	0.8597	pathogenic	0.281	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
D/K	0.8686	likely_pathogenic	0.8438	pathogenic	0.257	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
D/L	0.801	likely_pathogenic	0.7625	pathogenic	0.281	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/M	0.9323	likely_pathogenic	0.9097	pathogenic	0.293	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/N	0.2491	likely_benign	0.2101	benign	-0.166	Destabilizing	1.0	D	0.763	deleterious	N	0.47910955	None	None	N
D/P	0.9697	likely_pathogenic	0.9585	pathogenic	0.127	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
D/Q	0.7649	likely_pathogenic	0.7133	pathogenic	-0.105	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
D/R	0.8717	likely_pathogenic	0.8406	pathogenic	0.506	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/S	0.4184	ambiguous	0.3617	ambiguous	-0.261	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
D/T	0.7714	likely_pathogenic	0.7249	pathogenic	-0.086	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/V	0.7787	likely_pathogenic	0.6923	pathogenic	0.127	Stabilizing	1.0	D	0.841	deleterious	N	0.479558311	None	None	N
D/W	0.9797	likely_pathogenic	0.9746	pathogenic	0.108	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
D/Y	0.5738	likely_pathogenic	0.5116	ambiguous	0.194	Stabilizing	1.0	D	0.848	deleterious	N	0.497916056	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.