TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25200	75823;75824;75825	chr2:178570534;178570533;178570532	chr2:179435261;179435260;179435259
N2AB	23559	70900;70901;70902	chr2:178570534;178570533;178570532	chr2:179435261;179435260;179435259
N2A	22632	68119;68120;68121	chr2:178570534;178570533;178570532	chr2:179435261;179435260;179435259
N2B	16135	48628;48629;48630	chr2:178570534;178570533;178570532	chr2:179435261;179435260;179435259
Novex-1	16260	49003;49004;49005	chr2:178570534;178570533;178570532	chr2:179435261;179435260;179435259
Novex-2	16327	49204;49205;49206	chr2:178570534;178570533;178570532	chr2:179435261;179435260;179435259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-134
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.5626
• 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
K/M	None	None	1.0	N	0.661	0.604	0.473695954338	gnomAD-4.0.0	1.36882E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79921E-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
K/A	0.6315	likely_pathogenic	0.6746	pathogenic	-0.418	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
K/C	0.7381	likely_pathogenic	0.7873	pathogenic	-0.575	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.8635	likely_pathogenic	0.8839	pathogenic	0.115	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/E	0.4174	ambiguous	0.454	ambiguous	0.209	Stabilizing	0.999	D	0.681	prob.neutral	N	0.512894916	None	None	N
K/F	0.8708	likely_pathogenic	0.9017	pathogenic	-0.188	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
K/G	0.8666	likely_pathogenic	0.8865	pathogenic	-0.756	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/H	0.374	ambiguous	0.4191	ambiguous	-1.037	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/I	0.3924	ambiguous	0.4347	ambiguous	0.438	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/L	0.455	ambiguous	0.507	ambiguous	0.438	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/M	0.2829	likely_benign	0.3209	benign	0.211	Stabilizing	1.0	D	0.661	neutral	N	0.507688286	None	None	N
K/N	0.6875	likely_pathogenic	0.7186	pathogenic	-0.331	Destabilizing	1.0	D	0.764	deleterious	N	0.50333407	None	None	N
K/P	0.9907	likely_pathogenic	0.9919	pathogenic	0.183	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/Q	0.2178	likely_benign	0.2347	benign	-0.407	Destabilizing	1.0	D	0.757	deleterious	N	0.483401832	None	None	N
K/R	0.0945	likely_benign	0.0996	benign	-0.476	Destabilizing	0.999	D	0.611	neutral	N	0.481593361	None	None	N
K/S	0.6918	likely_pathogenic	0.7326	pathogenic	-0.992	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
K/T	0.2519	likely_benign	0.2752	benign	-0.698	Destabilizing	1.0	D	0.739	prob.delet.	N	0.497656104	None	None	N
K/V	0.3545	ambiguous	0.4022	ambiguous	0.183	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/W	0.8459	likely_pathogenic	0.8827	pathogenic	-0.075	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/Y	0.7747	likely_pathogenic	0.8196	pathogenic	0.226	Stabilizing	1.0	D	0.716	prob.delet.	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.