TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7103	21532;21533;21534	chr2:178723952;178723951;178723950	chr2:179588679;179588678;179588677
N2AB	6786	20581;20582;20583	chr2:178723952;178723951;178723950	chr2:179588679;179588678;179588677
N2A	5859	17800;17801;17802	chr2:178723952;178723951;178723950	chr2:179588679;179588678;179588677
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-55
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0804
• 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
L/M	rs1235519093	-1.765	0.454	N	0.43	0.111	0.421184727016	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/M	rs1235519093	-1.765	0.454	N	0.43	0.111	0.421184727016	gnomAD-4.0.0	2.73728E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5984E-06	0	0
L/V	None	None	0.005	N	0.309	0.078	0.190952846119	gnomAD-4.0.0	6.84319E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99601E-07	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
L/A	0.6435	likely_pathogenic	0.6555	pathogenic	-3.138	Highly Destabilizing	0.525	D	0.687	prob.neutral	None	None	None	None	N
L/C	0.6778	likely_pathogenic	0.6809	pathogenic	-2.597	Highly Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
L/D	0.9734	likely_pathogenic	0.9757	pathogenic	-3.752	Highly Destabilizing	0.991	D	0.892	deleterious	None	None	None	None	N
L/E	0.8544	likely_pathogenic	0.8685	pathogenic	-3.462	Highly Destabilizing	0.974	D	0.867	deleterious	None	None	None	None	N
L/F	0.2558	likely_benign	0.2594	benign	-1.861	Destabilizing	0.934	D	0.697	prob.neutral	N	0.487102043	None	None	N
L/G	0.8781	likely_pathogenic	0.8866	pathogenic	-3.726	Highly Destabilizing	0.974	D	0.854	deleterious	None	None	None	None	N
L/H	0.684	likely_pathogenic	0.7088	pathogenic	-3.215	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
L/I	0.0836	likely_benign	0.0826	benign	-1.378	Destabilizing	0.007	N	0.329	neutral	None	None	None	None	N
L/K	0.7777	likely_pathogenic	0.7885	pathogenic	-2.448	Highly Destabilizing	0.974	D	0.825	deleterious	None	None	None	None	N
L/M	0.138	likely_benign	0.1451	benign	-1.59	Destabilizing	0.454	N	0.43	neutral	N	0.484949222	None	None	N
L/N	0.8646	likely_pathogenic	0.872	pathogenic	-3.043	Highly Destabilizing	0.991	D	0.89	deleterious	None	None	None	None	N
L/P	0.9504	likely_pathogenic	0.9474	pathogenic	-1.954	Destabilizing	0.991	D	0.892	deleterious	None	None	None	None	N
L/Q	0.5911	likely_pathogenic	0.6202	pathogenic	-2.78	Highly Destabilizing	0.974	D	0.877	deleterious	None	None	None	None	N
L/R	0.6602	likely_pathogenic	0.6788	pathogenic	-2.252	Highly Destabilizing	0.974	D	0.878	deleterious	None	None	None	None	N
L/S	0.8094	likely_pathogenic	0.8322	pathogenic	-3.684	Highly Destabilizing	0.966	D	0.827	deleterious	N	0.513057111	None	None	N
L/T	0.6737	likely_pathogenic	0.6998	pathogenic	-3.241	Highly Destabilizing	0.842	D	0.736	prob.delet.	None	None	None	None	N
L/V	0.0897	likely_benign	0.0917	benign	-1.954	Destabilizing	0.005	N	0.309	neutral	N	0.440802744	None	None	N
L/W	0.5603	ambiguous	0.5767	pathogenic	-2.285	Highly Destabilizing	0.997	D	0.871	deleterious	D	0.52483149	None	None	N
L/Y	0.6552	likely_pathogenic	0.6673	pathogenic	-2.119	Highly Destabilizing	0.974	D	0.815	deleterious	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.