TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9634	29125;29126;29127	chr2:178707667;178707666;178707665	chr2:179572394;179572393;179572392
N2AB	9317	28174;28175;28176	chr2:178707667;178707666;178707665	chr2:179572394;179572393;179572392
N2A	8390	25393;25394;25395	chr2:178707667;178707666;178707665	chr2:179572394;179572393;179572392
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-82
• Domain position: 45
• Structural Position: 109
• Q(SASA): 0.4951
• 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	rs2076081318	None	0.003	None	0.148	0.076	0.255777322467	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
D/E	rs2076081318	None	0.003	None	0.148	0.076	0.255777322467	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8577E-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	0.1708	likely_benign	0.1443	benign	0.107	Stabilizing	0.028	N	0.219	neutral	None	None	None	None	N
D/C	0.7753	likely_pathogenic	0.6833	pathogenic	-0.074	Destabilizing	0.996	D	0.323	neutral	None	None	None	None	N
D/E	0.1361	likely_benign	0.1356	benign	-0.35	Destabilizing	0.003	N	0.148	neutral	None	None	None	None	N
D/F	0.675	likely_pathogenic	0.5765	pathogenic	-0.096	Destabilizing	0.984	D	0.33	neutral	None	None	None	None	N
D/G	0.1616	likely_benign	0.133	benign	0.033	Stabilizing	0.003	N	0.147	neutral	None	None	None	None	N
D/H	0.3317	likely_benign	0.2624	benign	0.501	Stabilizing	0.939	D	0.267	neutral	None	None	None	None	N
D/I	0.4415	ambiguous	0.3581	ambiguous	0.229	Stabilizing	0.953	D	0.367	neutral	None	None	None	None	N
D/K	0.3598	ambiguous	0.2994	benign	0.434	Stabilizing	0.59	D	0.292	neutral	None	None	None	None	N
D/L	0.4124	ambiguous	0.3274	benign	0.229	Stabilizing	0.742	D	0.364	neutral	None	None	None	None	N
D/M	0.6806	likely_pathogenic	0.6124	pathogenic	0.052	Stabilizing	0.996	D	0.327	neutral	None	None	None	None	N
D/N	0.1113	likely_benign	0.0963	benign	0.327	Stabilizing	0.007	N	0.145	neutral	None	None	None	None	N
D/P	0.4571	ambiguous	0.4226	ambiguous	0.206	Stabilizing	0.953	D	0.324	neutral	None	None	None	None	N
D/Q	0.3341	likely_benign	0.2899	benign	0.302	Stabilizing	0.59	D	0.265	neutral	None	None	None	None	N
D/R	0.4128	ambiguous	0.3368	benign	0.586	Stabilizing	0.91	D	0.362	neutral	None	None	None	None	N
D/S	0.1071	likely_benign	0.0969	benign	0.215	Stabilizing	0.373	N	0.192	neutral	None	None	None	None	N
D/T	0.2703	likely_benign	0.2294	benign	0.279	Stabilizing	0.742	D	0.287	neutral	None	None	None	None	N
D/V	0.2664	likely_benign	0.211	benign	0.206	Stabilizing	0.684	D	0.368	neutral	None	None	None	None	N
D/W	0.9168	likely_pathogenic	0.8794	pathogenic	-0.111	Destabilizing	0.996	D	0.417	neutral	None	None	None	None	N
D/Y	0.3364	likely_benign	0.2697	benign	0.115	Stabilizing	0.979	D	0.327	neutral	None	None	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.