TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19037	57334;57335;57336	chr2:178598508;178598507;178598506	chr2:179463235;179463234;179463233
N2AB	17396	52411;52412;52413	chr2:178598508;178598507;178598506	chr2:179463235;179463234;179463233
N2A	16469	49630;49631;49632	chr2:178598508;178598507;178598506	chr2:179463235;179463234;179463233
N2B	9972	30139;30140;30141	chr2:178598508;178598507;178598506	chr2:179463235;179463234;179463233
Novex-1	10097	30514;30515;30516	chr2:178598508;178598507;178598506	chr2:179463235;179463234;179463233
Novex-2	10164	30715;30716;30717	chr2:178598508;178598507;178598506	chr2:179463235;179463234;179463233
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: Fn3-26
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3269
• 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	rs1400944262	0.337	0.201	N	0.556	0.118	0.305730143919	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs1400944262	0.337	0.201	N	0.556	0.118	0.305730143919	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs1400944262	0.337	0.201	N	0.556	0.118	0.305730143919	gnomAD-4.0.0	6.57618E-06	None	None	None	None	N	None	2.41336E-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	0.2618	likely_benign	0.2779	benign	-0.355	Destabilizing	0.25	N	0.597	neutral	None	None	None	None	N
K/C	0.6029	likely_pathogenic	0.612	pathogenic	-0.394	Destabilizing	0.982	D	0.745	deleterious	None	None	None	None	N
K/D	0.6674	likely_pathogenic	0.6742	pathogenic	0.095	Stabilizing	0.7	D	0.664	neutral	None	None	None	None	N
K/E	0.1947	likely_benign	0.1954	benign	0.17	Stabilizing	0.201	N	0.556	neutral	N	0.469186132	None	None	N
K/F	0.6094	likely_pathogenic	0.6622	pathogenic	-0.147	Destabilizing	0.982	D	0.752	deleterious	None	None	None	None	N
K/G	0.473	ambiguous	0.4792	ambiguous	-0.681	Destabilizing	0.399	N	0.643	neutral	None	None	None	None	N
K/H	0.3278	likely_benign	0.3449	ambiguous	-1.025	Destabilizing	0.898	D	0.69	prob.neutral	None	None	None	None	N
K/I	0.201	likely_benign	0.2198	benign	0.464	Stabilizing	0.826	D	0.76	deleterious	None	None	None	None	N
K/L	0.2226	likely_benign	0.2653	benign	0.464	Stabilizing	0.399	N	0.643	neutral	None	None	None	None	N
K/M	0.1579	likely_benign	0.1703	benign	0.302	Stabilizing	0.931	D	0.689	prob.neutral	N	0.467609803	None	None	N
K/N	0.4394	ambiguous	0.4628	ambiguous	-0.145	Destabilizing	0.638	D	0.605	neutral	N	0.513651772	None	None	N
K/P	0.4071	ambiguous	0.4363	ambiguous	0.222	Stabilizing	0.826	D	0.709	prob.delet.	None	None	None	None	N
K/Q	0.1318	likely_benign	0.1399	benign	-0.269	Destabilizing	0.004	N	0.313	neutral	N	0.484849018	None	None	N
K/R	0.0783	likely_benign	0.0786	benign	-0.45	Destabilizing	0.002	N	0.364	neutral	N	0.436903142	None	None	N
K/S	0.4356	ambiguous	0.4502	ambiguous	-0.779	Destabilizing	0.25	N	0.579	neutral	None	None	None	None	N
K/T	0.1498	likely_benign	0.1533	benign	-0.514	Destabilizing	0.638	D	0.65	neutral	N	0.464012386	None	None	N
K/V	0.2059	likely_benign	0.2301	benign	0.222	Stabilizing	0.7	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.6009	likely_pathogenic	0.6234	pathogenic	-0.03	Destabilizing	0.982	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.5209	ambiguous	0.5449	ambiguous	0.258	Stabilizing	0.826	D	0.738	prob.delet.	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.