TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8989	27190;27191;27192	chr2:178713169;178713168;178713167	chr2:179577896;179577895;179577894
N2AB	8672	26239;26240;26241	chr2:178713169;178713168;178713167	chr2:179577896;179577895;179577894
N2A	7745	23458;23459;23460	chr2:178713169;178713168;178713167	chr2:179577896;179577895;179577894
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-75
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.5327
• 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/D	None	None	0.002	N	0.106	0.066	0.212008924253	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79898E-06	0	0
E/G	None	None	0.001	N	0.15	0.173	0.3571064206	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.1281	likely_benign	0.1298	benign	-0.69	Destabilizing	0.002	N	0.126	neutral	N	0.465450472	None	None	N
E/C	0.7299	likely_pathogenic	0.7445	pathogenic	-0.109	Destabilizing	0.983	D	0.325	neutral	None	None	None	None	N
E/D	0.1154	likely_benign	0.1187	benign	-0.435	Destabilizing	0.002	N	0.106	neutral	N	0.41417629	None	None	N
E/F	0.6566	likely_pathogenic	0.6488	pathogenic	-0.396	Destabilizing	0.94	D	0.351	neutral	None	None	None	None	N
E/G	0.1087	likely_benign	0.1146	benign	-0.936	Destabilizing	0.001	N	0.15	neutral	N	0.469010853	None	None	N
E/H	0.3129	likely_benign	0.2988	benign	-0.328	Destabilizing	0.836	D	0.283	neutral	None	None	None	None	N
E/I	0.3291	likely_benign	0.3346	benign	-0.054	Destabilizing	0.716	D	0.394	neutral	None	None	None	None	N
E/K	0.0916	likely_benign	0.0977	benign	0.21	Stabilizing	0.007	N	0.137	neutral	N	0.39959084	None	None	N
E/L	0.2402	likely_benign	0.2434	benign	-0.054	Destabilizing	0.418	N	0.389	neutral	None	None	None	None	N
E/M	0.3326	likely_benign	0.3398	benign	0.232	Stabilizing	0.836	D	0.329	neutral	None	None	None	None	N
E/N	0.1846	likely_benign	0.1969	benign	-0.27	Destabilizing	0.01	N	0.155	neutral	None	None	None	None	N
E/P	0.7944	likely_pathogenic	0.7797	pathogenic	-0.246	Destabilizing	0.593	D	0.367	neutral	None	None	None	None	N
E/Q	0.0928	likely_benign	0.0921	benign	-0.202	Destabilizing	0.007	N	0.098	neutral	N	0.42956703	None	None	N
E/R	0.1515	likely_benign	0.1532	benign	0.398	Stabilizing	0.264	N	0.167	neutral	None	None	None	None	N
E/S	0.1416	likely_benign	0.1409	benign	-0.449	Destabilizing	0.129	N	0.195	neutral	None	None	None	None	N
E/T	0.16	likely_benign	0.163	benign	-0.236	Destabilizing	0.01	N	0.14	neutral	None	None	None	None	N
E/V	0.1803	likely_benign	0.1842	benign	-0.246	Destabilizing	0.213	N	0.39	neutral	N	0.434610277	None	None	N
E/W	0.7933	likely_pathogenic	0.7859	pathogenic	-0.147	Destabilizing	0.983	D	0.356	neutral	None	None	None	None	N
E/Y	0.5146	ambiguous	0.5152	ambiguous	-0.129	Destabilizing	0.94	D	0.341	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.