TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27445	82558;82559;82560	chr2:178563799;178563798;178563797	chr2:179428526;179428525;179428524
N2AB	25804	77635;77636;77637	chr2:178563799;178563798;178563797	chr2:179428526;179428525;179428524
N2A	24877	74854;74855;74856	chr2:178563799;178563798;178563797	chr2:179428526;179428525;179428524
N2B	18380	55363;55364;55365	chr2:178563799;178563798;178563797	chr2:179428526;179428525;179428524
Novex-1	18505	55738;55739;55740	chr2:178563799;178563798;178563797	chr2:179428526;179428525;179428524
Novex-2	18572	55939;55940;55941	chr2:178563799;178563798;178563797	chr2:179428526;179428525;179428524
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-87
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1189
• 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
M/T	None	None	0.002	N	0.383	0.284	0.503248607038	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
M/A	0.421	ambiguous	0.38	ambiguous	-2.577	Highly Destabilizing	0.103	N	0.546	neutral	None	None	None	None	N
M/C	0.6378	likely_pathogenic	0.6051	pathogenic	-2.4	Highly Destabilizing	0.965	D	0.699	prob.neutral	None	None	None	None	N
M/D	0.9502	likely_pathogenic	0.943	pathogenic	-2.3	Highly Destabilizing	0.561	D	0.685	prob.neutral	None	None	None	None	N
M/E	0.72	likely_pathogenic	0.6864	pathogenic	-2.116	Highly Destabilizing	0.209	N	0.648	neutral	None	None	None	None	N
M/F	0.4788	ambiguous	0.4866	ambiguous	-1.026	Destabilizing	0.722	D	0.609	neutral	None	None	None	None	N
M/G	0.7271	likely_pathogenic	0.6976	pathogenic	-3.0	Highly Destabilizing	0.345	N	0.669	neutral	None	None	None	None	N
M/H	0.6406	likely_pathogenic	0.6108	pathogenic	-2.45	Highly Destabilizing	0.901	D	0.689	prob.neutral	None	None	None	None	N
M/I	0.5824	likely_pathogenic	0.5046	ambiguous	-1.369	Destabilizing	0.166	N	0.521	neutral	N	0.434534841	None	None	N
M/K	0.2484	likely_benign	0.2411	benign	-1.809	Destabilizing	0.001	N	0.405	neutral	N	0.458102347	None	None	N
M/L	0.1991	likely_benign	0.2019	benign	-1.369	Destabilizing	0.036	N	0.431	neutral	N	0.445943913	None	None	N
M/N	0.6851	likely_pathogenic	0.6418	pathogenic	-2.0	Highly Destabilizing	0.561	D	0.671	neutral	None	None	None	None	N
M/P	0.9911	likely_pathogenic	0.991	pathogenic	-1.755	Destabilizing	0.722	D	0.658	neutral	None	None	None	None	N
M/Q	0.3052	likely_benign	0.2848	benign	-1.808	Destabilizing	0.561	D	0.587	neutral	None	None	None	None	N
M/R	0.2109	likely_benign	0.216	benign	-1.638	Destabilizing	0.326	N	0.672	neutral	N	0.383855304	None	None	N
M/S	0.3972	ambiguous	0.3518	ambiguous	-2.58	Highly Destabilizing	0.209	N	0.6	neutral	None	None	None	None	N
M/T	0.2032	likely_benign	0.1705	benign	-2.292	Highly Destabilizing	0.002	N	0.383	neutral	N	0.462124087	None	None	N
M/V	0.1594	likely_benign	0.1232	benign	-1.755	Destabilizing	0.001	N	0.21	neutral	N	0.448290785	None	None	N
M/W	0.7953	likely_pathogenic	0.8067	pathogenic	-1.293	Destabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	N
M/Y	0.7376	likely_pathogenic	0.7383	pathogenic	-1.342	Destabilizing	0.965	D	0.709	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.