TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17191	51796;51797;51798	chr2:178609852;178609851;178609850	chr2:179474579;179474578;179474577
N2AB	15550	46873;46874;46875	chr2:178609852;178609851;178609850	chr2:179474579;179474578;179474577
N2A	14623	44092;44093;44094	chr2:178609852;178609851;178609850	chr2:179474579;179474578;179474577
N2B	8126	24601;24602;24603	chr2:178609852;178609851;178609850	chr2:179474579;179474578;179474577
Novex-1	8251	24976;24977;24978	chr2:178609852;178609851;178609850	chr2:179474579;179474578;179474577
Novex-2	8318	25177;25178;25179	chr2:178609852;178609851;178609850	chr2:179474579;179474578;179474577
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-13
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.367
• 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
E/K	None	None	0.012	N	0.197	0.137	0.211220785272	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	1.26695E-04	0	None	0	0	None	0	0	0	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
E/A	0.2106	likely_benign	0.2003	benign	-0.482	Destabilizing	0.454	N	0.277	neutral	N	0.460950651	None	None	N
E/C	0.8803	likely_pathogenic	0.865	pathogenic	-0.193	Destabilizing	0.998	D	0.448	neutral	None	None	None	None	N
E/D	0.1448	likely_benign	0.1437	benign	-0.481	Destabilizing	0.012	N	0.163	neutral	N	0.40742281	None	None	N
E/F	0.8645	likely_pathogenic	0.8439	pathogenic	-0.199	Destabilizing	0.991	D	0.409	neutral	None	None	None	None	N
E/G	0.1838	likely_benign	0.1574	benign	-0.713	Destabilizing	0.005	N	0.194	neutral	N	0.400670196	None	None	N
E/H	0.6214	likely_pathogenic	0.5968	pathogenic	-0.006	Destabilizing	0.991	D	0.264	neutral	None	None	None	None	N
E/I	0.6155	likely_pathogenic	0.5734	pathogenic	0.103	Stabilizing	0.974	D	0.411	neutral	None	None	None	None	N
E/K	0.2315	likely_benign	0.2046	benign	0.181	Stabilizing	0.012	N	0.197	neutral	N	0.465721752	None	None	N
E/L	0.5458	ambiguous	0.5192	ambiguous	0.103	Stabilizing	0.949	D	0.397	neutral	None	None	None	None	N
E/M	0.5588	ambiguous	0.5367	ambiguous	0.177	Stabilizing	0.998	D	0.381	neutral	None	None	None	None	N
E/N	0.3068	likely_benign	0.2891	benign	-0.254	Destabilizing	0.842	D	0.201	neutral	None	None	None	None	N
E/P	0.8842	likely_pathogenic	0.8731	pathogenic	-0.072	Destabilizing	0.974	D	0.321	neutral	None	None	None	None	N
E/Q	0.1823	likely_benign	0.1673	benign	-0.198	Destabilizing	0.801	D	0.314	neutral	N	0.490060049	None	None	N
E/R	0.4019	ambiguous	0.3646	ambiguous	0.445	Stabilizing	0.728	D	0.264	neutral	None	None	None	None	N
E/S	0.2182	likely_benign	0.2026	benign	-0.409	Destabilizing	0.688	D	0.227	neutral	None	None	None	None	N
E/T	0.2675	likely_benign	0.2453	benign	-0.219	Destabilizing	0.842	D	0.329	neutral	None	None	None	None	N
E/V	0.3676	ambiguous	0.3349	benign	-0.072	Destabilizing	0.966	D	0.367	neutral	N	0.45993193	None	None	N
E/W	0.947	likely_pathogenic	0.9395	pathogenic	0.009	Stabilizing	0.998	D	0.495	neutral	None	None	None	None	N
E/Y	0.7878	likely_pathogenic	0.7576	pathogenic	0.054	Stabilizing	0.991	D	0.375	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.