TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35181	105766;105767;105768	chr2:178531074;178531073;178531072	chr2:179395801;179395800;179395799
N2AB	33540	100843;100844;100845	chr2:178531074;178531073;178531072	chr2:179395801;179395800;179395799
N2A	32613	98062;98063;98064	chr2:178531074;178531073;178531072	chr2:179395801;179395800;179395799
N2B	26116	78571;78572;78573	chr2:178531074;178531073;178531072	chr2:179395801;179395800;179395799
Novex-1	26241	78946;78947;78948	chr2:178531074;178531073;178531072	chr2:179395801;179395800;179395799
Novex-2	26308	79147;79148;79149	chr2:178531074;178531073;178531072	chr2:179395801;179395800;179395799
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-164
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.6696
• 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
K/E	rs903998878	None	0.001	N	0.083	0.08	0.158396225186	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
K/E	rs903998878	None	0.001	N	0.083	0.08	0.158396225186	gnomAD-4.0.0	6.56978E-06	None	None	None	None	N	None	2.4122E-05	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
K/A	0.4123	ambiguous	0.4422	ambiguous	-0.247	Destabilizing	0.276	N	0.305	neutral	None	None	None	None	N
K/C	0.8783	likely_pathogenic	0.8965	pathogenic	-0.576	Destabilizing	0.987	D	0.214	neutral	None	None	None	None	N
K/D	0.6798	likely_pathogenic	0.6965	pathogenic	-0.089	Destabilizing	0.16	N	0.323	neutral	None	None	None	None	N
K/E	0.2978	likely_benign	0.2976	benign	-0.045	Destabilizing	0.001	N	0.083	neutral	N	0.444681971	None	None	N
K/F	0.9322	likely_pathogenic	0.9383	pathogenic	-0.392	Destabilizing	0.952	D	0.227	neutral	None	None	None	None	N
K/G	0.6033	likely_pathogenic	0.6427	pathogenic	-0.465	Destabilizing	0.481	N	0.292	neutral	None	None	None	None	N
K/H	0.5377	ambiguous	0.5481	ambiguous	-0.626	Destabilizing	0.868	D	0.22	neutral	None	None	None	None	N
K/I	0.6112	likely_pathogenic	0.6048	pathogenic	0.261	Stabilizing	0.868	D	0.271	neutral	None	None	None	None	N
K/L	0.5423	ambiguous	0.5444	ambiguous	0.261	Stabilizing	0.481	N	0.301	neutral	None	None	None	None	N
K/M	0.4416	ambiguous	0.426	ambiguous	-0.145	Destabilizing	0.832	D	0.217	neutral	N	0.454793515	None	None	N
K/N	0.5592	ambiguous	0.5526	ambiguous	-0.247	Destabilizing	0.411	N	0.232	neutral	N	0.42590421	None	None	N
K/P	0.5651	likely_pathogenic	0.6139	pathogenic	0.119	Stabilizing	0.652	D	0.325	neutral	None	None	None	None	N
K/Q	0.224	likely_benign	0.2263	benign	-0.303	Destabilizing	0.001	N	0.083	neutral	N	0.423885412	None	None	N
K/R	0.1007	likely_benign	0.1067	benign	-0.229	Destabilizing	0.126	N	0.255	neutral	N	0.500575327	None	None	N
K/S	0.5314	ambiguous	0.5524	ambiguous	-0.698	Destabilizing	0.276	N	0.275	neutral	None	None	None	None	N
K/T	0.2624	likely_benign	0.2764	benign	-0.489	Destabilizing	0.411	N	0.307	neutral	N	0.496708302	None	None	N
K/V	0.5575	ambiguous	0.5633	ambiguous	0.119	Stabilizing	0.652	D	0.321	neutral	None	None	None	None	N
K/W	0.9084	likely_pathogenic	0.9228	pathogenic	-0.431	Destabilizing	0.987	D	0.221	neutral	None	None	None	None	N
K/Y	0.8248	likely_pathogenic	0.8292	pathogenic	-0.093	Destabilizing	0.952	D	0.263	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.