TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9256	27991;27992;27993	chr2:178712064;178712063;178712062	chr2:179576791;179576790;179576789
N2AB	8939	27040;27041;27042	chr2:178712064;178712063;178712062	chr2:179576791;179576790;179576789
N2A	8012	24259;24260;24261	chr2:178712064;178712063;178712062	chr2:179576791;179576790;179576789
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-78
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.5217
• 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
R/S	None	None	0.001	N	0.154	0.136	0.203808441222	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85835E-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
R/A	0.2622	likely_benign	0.3787	ambiguous	0.245	Stabilizing	0.002	N	0.201	neutral	None	None	None	None	N
R/C	0.1777	likely_benign	0.262	benign	0.192	Stabilizing	0.497	N	0.283	neutral	None	None	None	None	N
R/D	0.5456	ambiguous	0.6758	pathogenic	-0.083	Destabilizing	0.018	N	0.283	neutral	None	None	None	None	N
R/E	0.2371	likely_benign	0.3188	benign	-0.015	Destabilizing	0.009	N	0.193	neutral	None	None	None	None	N
R/F	0.458	ambiguous	0.5978	pathogenic	0.06	Stabilizing	None	N	0.202	neutral	None	None	None	None	N
R/G	0.1742	likely_benign	0.2814	benign	0.049	Stabilizing	0.014	N	0.225	neutral	N	0.515396503	None	None	N
R/H	0.1006	likely_benign	0.1247	benign	-0.619	Destabilizing	0.245	N	0.211	neutral	None	None	None	None	N
R/I	0.1768	likely_benign	0.2407	benign	0.728	Stabilizing	0.009	N	0.291	neutral	None	None	None	None	N
R/K	0.0745	likely_benign	0.0882	benign	0.239	Stabilizing	None	N	0.107	neutral	N	0.444995055	None	None	N
R/L	0.1956	likely_benign	0.2609	benign	0.728	Stabilizing	0.004	N	0.229	neutral	None	None	None	None	N
R/M	0.1747	likely_benign	0.2458	benign	0.187	Stabilizing	0.196	N	0.253	neutral	N	0.517994091	None	None	N
R/N	0.4002	ambiguous	0.5216	ambiguous	0.465	Stabilizing	0.018	N	0.163	neutral	None	None	None	None	N
R/P	0.761	likely_pathogenic	0.8591	pathogenic	0.588	Stabilizing	0.085	N	0.357	neutral	None	None	None	None	N
R/Q	0.0787	likely_benign	0.095	benign	0.41	Stabilizing	0.022	N	0.197	neutral	None	None	None	None	N
R/S	0.2695	likely_benign	0.397	ambiguous	0.258	Stabilizing	0.001	N	0.154	neutral	N	0.45036359	None	None	N
R/T	0.1316	likely_benign	0.1785	benign	0.454	Stabilizing	None	N	0.151	neutral	N	0.439954595	None	None	N
R/V	0.2521	likely_benign	0.3239	benign	0.588	Stabilizing	None	N	0.175	neutral	None	None	None	None	N
R/W	0.1396	likely_benign	0.2048	benign	-0.073	Destabilizing	0.427	N	0.28	neutral	N	0.510268726	None	None	N
R/Y	0.3276	likely_benign	0.4501	ambiguous	0.343	Stabilizing	None	N	0.165	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.