TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25241	75946;75947;75948	chr2:178570411;178570410;178570409	chr2:179435138;179435137;179435136
N2AB	23600	71023;71024;71025	chr2:178570411;178570410;178570409	chr2:179435138;179435137;179435136
N2A	22673	68242;68243;68244	chr2:178570411;178570410;178570409	chr2:179435138;179435137;179435136
N2B	16176	48751;48752;48753	chr2:178570411;178570410;178570409	chr2:179435138;179435137;179435136
Novex-1	16301	49126;49127;49128	chr2:178570411;178570410;178570409	chr2:179435138;179435137;179435136
Novex-2	16368	49327;49328;49329	chr2:178570411;178570410;178570409	chr2:179435138;179435137;179435136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-71
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.2263
• 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
I/T	rs752485989	-2.755	0.379	N	0.568	0.144	0.610711448424	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.91E-05	None	9.99E-05	5.63E-05	None	0	None	0	0	0
I/T	rs752485989	-2.755	0.379	N	0.568	0.144	0.610711448424	gnomAD-4.0.0	7.5292E-06	None	None	None	None	N	None	0	2.23754E-05	None	3.82907E-05	5.05894E-05	None	0	0	5.39763E-06	0	1.65733E-05

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
I/A	0.4202	ambiguous	0.4877	ambiguous	-2.633	Highly Destabilizing	0.25	N	0.564	neutral	None	None	None	None	N
I/C	0.7401	likely_pathogenic	0.7806	pathogenic	-1.908	Destabilizing	0.977	D	0.625	neutral	None	None	None	None	N
I/D	0.9319	likely_pathogenic	0.945	pathogenic	-3.255	Highly Destabilizing	0.85	D	0.693	prob.neutral	None	None	None	None	N
I/E	0.7875	likely_pathogenic	0.8224	pathogenic	-3.11	Highly Destabilizing	0.85	D	0.678	prob.neutral	None	None	None	None	N
I/F	0.3453	ambiguous	0.3711	ambiguous	-1.61	Destabilizing	0.81	D	0.58	neutral	N	0.469127059	None	None	N
I/G	0.8789	likely_pathogenic	0.9124	pathogenic	-3.077	Highly Destabilizing	0.617	D	0.657	neutral	None	None	None	None	N
I/H	0.6729	likely_pathogenic	0.7076	pathogenic	-2.477	Highly Destabilizing	0.992	D	0.717	prob.delet.	None	None	None	None	N
I/K	0.5197	ambiguous	0.5784	pathogenic	-2.116	Highly Destabilizing	0.85	D	0.679	prob.neutral	None	None	None	None	N
I/L	0.1943	likely_benign	0.2133	benign	-1.366	Destabilizing	0.099	N	0.445	neutral	N	0.504106782	None	None	N
I/M	0.1509	likely_benign	0.1608	benign	-1.244	Destabilizing	0.81	D	0.598	neutral	N	0.495891821	None	None	N
I/N	0.5725	likely_pathogenic	0.6078	pathogenic	-2.309	Highly Destabilizing	0.81	D	0.695	prob.neutral	N	0.465048454	None	None	N
I/P	0.9865	likely_pathogenic	0.9915	pathogenic	-1.77	Destabilizing	0.92	D	0.697	prob.neutral	None	None	None	None	N
I/Q	0.6233	likely_pathogenic	0.6511	pathogenic	-2.3	Highly Destabilizing	0.92	D	0.706	prob.neutral	None	None	None	None	N
I/R	0.3999	ambiguous	0.4692	ambiguous	-1.608	Destabilizing	0.92	D	0.707	prob.neutral	None	None	None	None	N
I/S	0.4351	ambiguous	0.4816	ambiguous	-2.87	Highly Destabilizing	0.099	N	0.536	neutral	N	0.519862881	None	None	N
I/T	0.1415	likely_benign	0.1654	benign	-2.616	Highly Destabilizing	0.379	N	0.568	neutral	N	0.511032755	None	None	N
I/V	0.0604	likely_benign	0.0679	benign	-1.77	Destabilizing	0.002	N	0.269	neutral	N	0.446541346	None	None	N
I/W	0.8975	likely_pathogenic	0.9082	pathogenic	-2.017	Highly Destabilizing	0.992	D	0.703	prob.neutral	None	None	None	None	N
I/Y	0.711	likely_pathogenic	0.7417	pathogenic	-1.81	Destabilizing	0.92	D	0.634	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.