TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34433	103522;103523;103524	chr2:178533318;178533317;178533316	chr2:179398045;179398044;179398043
N2AB	32792	98599;98600;98601	chr2:178533318;178533317;178533316	chr2:179398045;179398044;179398043
N2A	31865	95818;95819;95820	chr2:178533318;178533317;178533316	chr2:179398045;179398044;179398043
N2B	25368	76327;76328;76329	chr2:178533318;178533317;178533316	chr2:179398045;179398044;179398043
Novex-1	25493	76702;76703;76704	chr2:178533318;178533317;178533316	chr2:179398045;179398044;179398043
Novex-2	25560	76903;76904;76905	chr2:178533318;178533317;178533316	chr2:179398045;179398044;179398043
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: Ig-162
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.5886
• 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
Y/N	None	None	0.973	N	0.583	0.278	0.7264753701	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85768E-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
Y/A	0.7749	likely_pathogenic	0.7385	pathogenic	-1.613	Destabilizing	0.737	D	0.427	neutral	None	None	None	None	N
Y/C	0.3322	likely_benign	0.274	benign	-0.013	Destabilizing	0.998	D	0.519	neutral	N	0.516145865	None	None	N
Y/D	0.631	likely_pathogenic	0.5774	pathogenic	-0.009	Destabilizing	0.719	D	0.569	neutral	N	0.431700471	None	None	N
Y/E	0.8558	likely_pathogenic	0.831	pathogenic	0.008	Stabilizing	0.083	N	0.329	neutral	None	None	None	None	N
Y/F	0.1379	likely_benign	0.1228	benign	-0.909	Destabilizing	0.837	D	0.446	neutral	N	0.438301157	None	None	N
Y/G	0.8137	likely_pathogenic	0.778	pathogenic	-1.876	Destabilizing	0.932	D	0.539	neutral	None	None	None	None	N
Y/H	0.4663	ambiguous	0.4017	ambiguous	-0.629	Destabilizing	0.991	D	0.507	neutral	N	0.451153024	None	None	N
Y/I	0.5758	likely_pathogenic	0.5304	ambiguous	-0.865	Destabilizing	0.083	N	0.269	neutral	None	None	None	None	N
Y/K	0.8457	likely_pathogenic	0.8157	pathogenic	-0.289	Destabilizing	0.872	D	0.536	neutral	None	None	None	None	N
Y/L	0.5528	ambiguous	0.5386	ambiguous	-0.865	Destabilizing	0.009	N	0.262	neutral	None	None	None	None	N
Y/M	0.7265	likely_pathogenic	0.698	pathogenic	-0.378	Destabilizing	0.96	D	0.549	neutral	None	None	None	None	N
Y/N	0.348	ambiguous	0.3024	benign	-0.34	Destabilizing	0.973	D	0.583	neutral	N	0.422272911	None	None	N
Y/P	0.9601	likely_pathogenic	0.9483	pathogenic	-1.102	Destabilizing	0.993	D	0.571	neutral	None	None	None	None	N
Y/Q	0.7999	likely_pathogenic	0.7553	pathogenic	-0.365	Destabilizing	0.96	D	0.587	neutral	None	None	None	None	N
Y/R	0.726	likely_pathogenic	0.6847	pathogenic	0.111	Stabilizing	0.96	D	0.585	neutral	None	None	None	None	N
Y/S	0.4481	ambiguous	0.4033	ambiguous	-0.822	Destabilizing	0.837	D	0.537	neutral	N	0.417539095	None	None	N
Y/T	0.554	ambiguous	0.5247	ambiguous	-0.713	Destabilizing	0.872	D	0.528	neutral	None	None	None	None	N
Y/V	0.4919	ambiguous	0.4568	ambiguous	-1.102	Destabilizing	0.037	N	0.277	neutral	None	None	None	None	N
Y/W	0.6035	likely_pathogenic	0.576	pathogenic	-0.785	Destabilizing	0.998	D	0.501	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.