TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7239	21940;21941;21942	chr2:178723292;178723291;178723290	chr2:179588019;179588018;179588017
N2AB	6922	20989;20990;20991	chr2:178723292;178723291;178723290	chr2:179588019;179588018;179588017
N2A	5995	18208;18209;18210	chr2:178723292;178723291;178723290	chr2:179588019;179588018;179588017
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-57
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.317
• 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
H/R	None	None	0.007	N	0.279	0.111	0.165133752707	gnomAD-4.0.0	3.1845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71922E-06	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
H/A	0.2038	likely_benign	0.2131	benign	-0.341	Destabilizing	0.002	N	0.309	neutral	None	None	None	None	N
H/C	0.1345	likely_benign	0.1507	benign	0.059	Stabilizing	0.497	N	0.455	neutral	None	None	None	None	N
H/D	0.1963	likely_benign	0.2271	benign	0.105	Stabilizing	0.007	N	0.317	neutral	N	0.494058439	None	None	N
H/E	0.2269	likely_benign	0.2568	benign	0.168	Stabilizing	0.004	N	0.221	neutral	None	None	None	None	N
H/F	0.1684	likely_benign	0.1795	benign	0.515	Stabilizing	0.009	N	0.418	neutral	None	None	None	None	N
H/G	0.2789	likely_benign	0.2988	benign	-0.665	Destabilizing	0.008	N	0.28	neutral	None	None	None	None	N
H/I	0.1407	likely_benign	0.1537	benign	0.518	Stabilizing	None	N	0.273	neutral	None	None	None	None	N
H/K	0.1972	likely_benign	0.2084	benign	-0.265	Destabilizing	0.004	N	0.282	neutral	None	None	None	None	N
H/L	0.0872	likely_benign	0.0909	benign	0.518	Stabilizing	None	N	0.234	neutral	N	0.380231501	None	None	N
H/M	0.3201	likely_benign	0.3314	benign	0.267	Stabilizing	0.044	N	0.549	neutral	None	None	None	None	N
H/N	0.0909	likely_benign	0.1035	benign	-0.287	Destabilizing	None	N	0.067	neutral	N	0.504928793	None	None	N
H/P	0.4135	ambiguous	0.4398	ambiguous	0.256	Stabilizing	0.065	N	0.52	neutral	N	0.504928793	None	None	N
H/Q	0.1248	likely_benign	0.1398	benign	-0.12	Destabilizing	None	N	0.054	neutral	N	0.394606307	None	None	N
H/R	0.0912	likely_benign	0.0969	benign	-0.737	Destabilizing	0.007	N	0.279	neutral	N	0.446939282	None	None	N
H/S	0.1618	likely_benign	0.1774	benign	-0.429	Destabilizing	0.001	N	0.113	neutral	None	None	None	None	N
H/T	0.1617	likely_benign	0.1724	benign	-0.252	Destabilizing	0.008	N	0.271	neutral	None	None	None	None	N
H/V	0.126	likely_benign	0.1336	benign	0.256	Stabilizing	None	N	0.248	neutral	None	None	None	None	N
H/W	0.3604	ambiguous	0.3558	ambiguous	0.711	Stabilizing	0.245	N	0.429	neutral	None	None	None	None	N
H/Y	0.0625	likely_benign	0.0669	benign	0.921	Stabilizing	None	N	0.099	neutral	N	0.415058937	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.