TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18865	56818;56819;56820	chr2:178599200;178599199;178599198	chr2:179463927;179463926;179463925
N2AB	17224	51895;51896;51897	chr2:178599200;178599199;178599198	chr2:179463927;179463926;179463925
N2A	16297	49114;49115;49116	chr2:178599200;178599199;178599198	chr2:179463927;179463926;179463925
N2B	9800	29623;29624;29625	chr2:178599200;178599199;178599198	chr2:179463927;179463926;179463925
Novex-1	9925	29998;29999;30000	chr2:178599200;178599199;178599198	chr2:179463927;179463926;179463925
Novex-2	9992	30199;30200;30201	chr2:178599200;178599199;178599198	chr2:179463927;179463926;179463925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-24
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.7243
• Predicted PPI site: I

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
Y/C	None	None	0.976	N	0.715	0.318	0.411665641125	gnomAD-4.0.0	6.59717E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.41779E-06	0	0
Y/F	None	None	0.002	N	0.32	0.067	0.269111216191	gnomAD-4.0.0	7.33019E-07	None	None	None	None	I	None	0	0	None	0	0	None	1.99593E-05	0	0	0	0
Y/H	rs749192204	0.421	0.781	N	0.591	0.38	0.326881540566	gnomAD-2.1.1	5.68E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.78E-05	None	0	0	0
Y/H	rs749192204	0.421	0.781	N	0.591	0.38	0.326881540566	gnomAD-4.0.0	5.86489E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.21569E-04	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
Y/A	0.9296	likely_pathogenic	0.8871	pathogenic	-0.715	Destabilizing	0.399	N	0.605	neutral	None	None	None	None	I
Y/C	0.5452	ambiguous	0.451	ambiguous	0.083	Stabilizing	0.976	D	0.715	prob.delet.	N	0.506763085	None	None	I
Y/D	0.8992	likely_pathogenic	0.8613	pathogenic	0.851	Stabilizing	0.916	D	0.681	prob.neutral	N	0.481329057	None	None	I
Y/E	0.969	likely_pathogenic	0.9516	pathogenic	0.834	Stabilizing	0.826	D	0.677	prob.neutral	None	None	None	None	I
Y/F	0.1134	likely_benign	0.1122	benign	-0.366	Destabilizing	0.002	N	0.32	neutral	N	0.478576406	None	None	I
Y/G	0.9263	likely_pathogenic	0.8876	pathogenic	-0.906	Destabilizing	0.826	D	0.661	neutral	None	None	None	None	I
Y/H	0.5854	likely_pathogenic	0.5038	ambiguous	0.189	Stabilizing	0.781	D	0.591	neutral	N	0.508051164	None	None	I
Y/I	0.773	likely_pathogenic	0.7073	pathogenic	-0.231	Destabilizing	0.539	D	0.602	neutral	None	None	None	None	I
Y/K	0.9522	likely_pathogenic	0.9216	pathogenic	0.167	Stabilizing	0.826	D	0.673	neutral	None	None	None	None	I
Y/L	0.7988	likely_pathogenic	0.7494	pathogenic	-0.231	Destabilizing	0.25	N	0.622	neutral	None	None	None	None	I
Y/M	0.8513	likely_pathogenic	0.7928	pathogenic	-0.105	Destabilizing	0.947	D	0.616	neutral	None	None	None	None	I
Y/N	0.6852	likely_pathogenic	0.6123	pathogenic	-0.024	Destabilizing	0.916	D	0.683	prob.neutral	N	0.515977214	None	None	I
Y/P	0.9941	likely_pathogenic	0.9902	pathogenic	-0.373	Destabilizing	0.935	D	0.695	prob.neutral	None	None	None	None	I
Y/Q	0.9351	likely_pathogenic	0.8973	pathogenic	0.021	Stabilizing	0.935	D	0.633	neutral	None	None	None	None	I
Y/R	0.905	likely_pathogenic	0.8549	pathogenic	0.43	Stabilizing	0.826	D	0.684	prob.neutral	None	None	None	None	I
Y/S	0.8522	likely_pathogenic	0.7898	pathogenic	-0.457	Destabilizing	0.781	D	0.657	neutral	N	0.516497289	None	None	I
Y/T	0.9294	likely_pathogenic	0.8909	pathogenic	-0.38	Destabilizing	0.826	D	0.662	neutral	None	None	None	None	I
Y/V	0.6955	likely_pathogenic	0.615	pathogenic	-0.373	Destabilizing	0.25	N	0.64	neutral	None	None	None	None	I
Y/W	0.5784	likely_pathogenic	0.5316	ambiguous	-0.474	Destabilizing	0.947	D	0.585	neutral	None	None	None	None	I

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.