TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2898	8917;8918;8919	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614
N2AB	2898	8917;8918;8919	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614
N2A	2898	8917;8918;8919	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614
N2B	2852	8779;8780;8781	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614
Novex-1	2852	8779;8780;8781	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614
Novex-2	2852	8779;8780;8781	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614
Novex-3	2898	8917;8918;8919	chr2:178769889;178769888;178769887	chr2:179634616;179634615;179634614

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-19
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.273
• 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
T/A	None	None	None	N	0.083	0.044	0.119812018005	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.0969	likely_benign	0.0868	benign	-0.578	Destabilizing	None	N	0.083	neutral	N	0.50517243	None	None	N
T/C	0.5767	likely_pathogenic	0.5544	ambiguous	-0.267	Destabilizing	0.676	D	0.397	neutral	None	None	None	None	N
T/D	0.5243	ambiguous	0.507	ambiguous	0.048	Stabilizing	0.038	N	0.383	neutral	None	None	None	None	N
T/E	0.3817	ambiguous	0.3879	ambiguous	0.008	Stabilizing	0.038	N	0.407	neutral	None	None	None	None	N
T/F	0.3951	ambiguous	0.3851	ambiguous	-0.818	Destabilizing	0.356	N	0.458	neutral	None	None	None	None	N
T/G	0.395	ambiguous	0.3546	ambiguous	-0.786	Destabilizing	0.016	N	0.357	neutral	None	None	None	None	N
T/H	0.4166	ambiguous	0.3805	ambiguous	-1.066	Destabilizing	0.356	N	0.417	neutral	None	None	None	None	N
T/I	0.2243	likely_benign	0.253	benign	-0.132	Destabilizing	0.029	N	0.397	neutral	D	0.591212644	None	None	N
T/K	0.3013	likely_benign	0.3225	benign	-0.539	Destabilizing	0.038	N	0.398	neutral	None	None	None	None	N
T/L	0.1458	likely_benign	0.1493	benign	-0.132	Destabilizing	0.016	N	0.373	neutral	None	None	None	None	N
T/M	0.0992	likely_benign	0.0974	benign	0.152	Stabilizing	0.356	N	0.406	neutral	None	None	None	None	N
T/N	0.1719	likely_benign	0.1414	benign	-0.336	Destabilizing	None	N	0.186	neutral	N	0.512268375	None	None	N
T/P	0.1426	likely_benign	0.1359	benign	-0.249	Destabilizing	0.171	N	0.463	neutral	N	0.514739675	None	None	N
T/Q	0.297	likely_benign	0.2914	benign	-0.549	Destabilizing	0.214	N	0.449	neutral	None	None	None	None	N
T/R	0.2672	likely_benign	0.2782	benign	-0.259	Destabilizing	0.214	N	0.454	neutral	None	None	None	None	N
T/S	0.1571	likely_benign	0.115	benign	-0.605	Destabilizing	None	N	0.115	neutral	N	0.475794998	None	None	N
T/V	0.1523	likely_benign	0.1739	benign	-0.249	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
T/W	0.7556	likely_pathogenic	0.728	pathogenic	-0.772	Destabilizing	0.864	D	0.477	neutral	None	None	None	None	N
T/Y	0.4181	ambiguous	0.3923	ambiguous	-0.53	Destabilizing	0.356	N	0.459	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.