TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33355	100288;100289;100290	chr2:178537046;178537045;178537044	chr2:179401773;179401772;179401771
N2AB	31714	95365;95366;95367	chr2:178537046;178537045;178537044	chr2:179401773;179401772;179401771
N2A	30787	92584;92585;92586	chr2:178537046;178537045;178537044	chr2:179401773;179401772;179401771
N2B	24290	73093;73094;73095	chr2:178537046;178537045;178537044	chr2:179401773;179401772;179401771
Novex-1	24415	73468;73469;73470	chr2:178537046;178537045;178537044	chr2:179401773;179401772;179401771
Novex-2	24482	73669;73670;73671	chr2:178537046;178537045;178537044	chr2:179401773;179401772;179401771
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-130
• Domain position: 66
• Structural Position: 96
• Q(SASA): 0.8639
• Predicted PPI site: I

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
N/T	None	None	0.998	N	0.585	0.497	0.355865052028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
N/A	0.5414	ambiguous	0.4362	ambiguous	-0.148	Destabilizing	0.997	D	0.549	neutral	None	None	None	None	I
N/C	0.6489	likely_pathogenic	0.5191	ambiguous	0.256	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
N/D	0.3273	likely_benign	0.2247	benign	0.19	Stabilizing	0.996	D	0.506	neutral	N	0.451387018	None	None	I
N/E	0.7559	likely_pathogenic	0.6504	pathogenic	0.136	Stabilizing	0.994	D	0.505	neutral	None	None	None	None	I
N/F	0.8845	likely_pathogenic	0.8101	pathogenic	-0.678	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
N/G	0.3493	ambiguous	0.2918	benign	-0.269	Destabilizing	0.998	D	0.481	neutral	None	None	None	None	I
N/H	0.2254	likely_benign	0.1811	benign	-0.272	Destabilizing	0.999	D	0.635	neutral	N	0.473001399	None	None	I
N/I	0.8204	likely_pathogenic	0.7114	pathogenic	0.072	Stabilizing	1.0	D	0.671	neutral	N	0.490398092	None	None	I
N/K	0.7017	likely_pathogenic	0.5919	pathogenic	0.167	Stabilizing	0.992	D	0.553	neutral	N	0.430379815	None	None	I
N/L	0.6658	likely_pathogenic	0.5579	ambiguous	0.072	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	I
N/M	0.7753	likely_pathogenic	0.6772	pathogenic	0.209	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	I
N/P	0.8415	likely_pathogenic	0.7636	pathogenic	0.023	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
N/Q	0.626	likely_pathogenic	0.5423	ambiguous	-0.23	Destabilizing	0.967	D	0.312	neutral	None	None	None	None	I
N/R	0.7113	likely_pathogenic	0.624	pathogenic	0.232	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	I
N/S	0.1492	likely_benign	0.1239	benign	-0.016	Destabilizing	0.996	D	0.471	neutral	N	0.505626935	None	None	I
N/T	0.4241	ambiguous	0.3283	benign	0.057	Stabilizing	0.998	D	0.585	neutral	N	0.478027829	None	None	I
N/V	0.8045	likely_pathogenic	0.6986	pathogenic	0.023	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
N/W	0.9497	likely_pathogenic	0.9186	pathogenic	-0.763	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
N/Y	0.4516	ambiguous	0.3529	ambiguous	-0.45	Destabilizing	1.0	D	0.642	neutral	N	0.496892552	None	None	I

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.