TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2751	8476;8477;8478	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266
N2AB	2751	8476;8477;8478	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266
N2A	2751	8476;8477;8478	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266
N2B	2705	8338;8339;8340	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266
Novex-1	2705	8338;8339;8340	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266
Novex-2	2705	8338;8339;8340	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266
Novex-3	2751	8476;8477;8478	chr2:178770541;178770540;178770539	chr2:179635268;179635267;179635266

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-17
• Domain position: 45
• Structural Position: 111
• Q(SASA): 0.6967
• 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/G	rs368235451	-0.086	0.024	N	0.335	0.241	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14863E-04	0	None	0	0	None	0	None	0	0	0
E/G	rs368235451	-0.086	0.024	N	0.335	0.241	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs368235451	-0.086	0.024	N	0.335	0.241	None	gnomAD-4.0.0	3.15978E-05	None	None	None	None	N	None	1.33461E-05	0	None	0	0	None	0	0	4.15251E-05	0	1.60031E-05

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	0.115	likely_benign	0.1339	benign	-0.048	Destabilizing	0.024	N	0.377	neutral	N	0.486149861	None	None	N
E/C	0.6486	likely_pathogenic	0.7491	pathogenic	-0.216	Destabilizing	0.864	D	0.293	neutral	None	None	None	None	N
E/D	0.0508	likely_benign	0.0551	benign	-0.32	Destabilizing	None	N	0.116	neutral	N	0.333749287	None	None	N
E/F	0.5953	likely_pathogenic	0.6807	pathogenic	-0.101	Destabilizing	0.628	D	0.317	neutral	None	None	None	None	N
E/G	0.0885	likely_benign	0.1047	benign	-0.153	Destabilizing	0.024	N	0.335	neutral	N	0.497586807	None	None	N
E/H	0.266	likely_benign	0.3264	benign	0.509	Stabilizing	0.356	N	0.297	neutral	None	None	None	None	N
E/I	0.2758	likely_benign	0.3561	ambiguous	0.17	Stabilizing	0.356	N	0.361	neutral	None	None	None	None	N
E/K	0.1135	likely_benign	0.1274	benign	0.369	Stabilizing	0.024	N	0.307	neutral	N	0.44169667	None	None	N
E/L	0.2908	likely_benign	0.3694	ambiguous	0.17	Stabilizing	0.072	N	0.385	neutral	None	None	None	None	N
E/M	0.3858	ambiguous	0.4675	ambiguous	-0.035	Destabilizing	0.864	D	0.305	neutral	None	None	None	None	N
E/N	0.0991	likely_benign	0.1175	benign	0.136	Stabilizing	0.016	N	0.303	neutral	None	None	None	None	N
E/P	0.2591	likely_benign	0.3267	benign	0.115	Stabilizing	0.136	N	0.361	neutral	None	None	None	None	N
E/Q	0.1228	likely_benign	0.1423	benign	0.147	Stabilizing	0.055	N	0.303	neutral	N	0.499506418	None	None	N
E/R	0.1889	likely_benign	0.2145	benign	0.591	Stabilizing	0.072	N	0.306	neutral	None	None	None	None	N
E/S	0.1005	likely_benign	0.1185	benign	-0.001	Destabilizing	0.016	N	0.304	neutral	None	None	None	None	N
E/T	0.1565	likely_benign	0.1916	benign	0.095	Stabilizing	0.072	N	0.351	neutral	None	None	None	None	N
E/V	0.1783	likely_benign	0.2259	benign	0.115	Stabilizing	0.106	N	0.407	neutral	N	0.514371176	None	None	N
E/W	0.7525	likely_pathogenic	0.8142	pathogenic	-0.061	Destabilizing	0.864	D	0.317	neutral	None	None	None	None	N
E/Y	0.4046	ambiguous	0.4768	ambiguous	0.115	Stabilizing	0.628	D	0.323	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.