TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23382	70369;70370;70371	chr2:178575988;178575987;178575986	chr2:179440715;179440714;179440713
N2AB	21741	65446;65447;65448	chr2:178575988;178575987;178575986	chr2:179440715;179440714;179440713
N2A	20814	62665;62666;62667	chr2:178575988;178575987;178575986	chr2:179440715;179440714;179440713
N2B	14317	43174;43175;43176	chr2:178575988;178575987;178575986	chr2:179440715;179440714;179440713
Novex-1	14442	43549;43550;43551	chr2:178575988;178575987;178575986	chr2:179440715;179440714;179440713
Novex-2	14509	43750;43751;43752	chr2:178575988;178575987;178575986	chr2:179440715;179440714;179440713
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: Ig-129
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.9079
• 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/D	None	None	None	N	0.12	0.102	0.0401082797425	gnomAD-4.0.0	1.59643E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87145E-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	0.1501	likely_benign	0.1657	benign	-0.094	Destabilizing	0.016	N	0.273	neutral	None	None	None	None	I
N/C	0.2458	likely_benign	0.288	benign	0.217	Stabilizing	0.864	D	0.331	neutral	None	None	None	None	I
N/D	0.0668	likely_benign	0.0675	benign	0.1	Stabilizing	None	N	0.12	neutral	N	0.405702296	None	None	I
N/E	0.1789	likely_benign	0.1905	benign	0.034	Stabilizing	0.016	N	0.245	neutral	None	None	None	None	I
N/F	0.4979	ambiguous	0.5556	ambiguous	-0.704	Destabilizing	0.628	D	0.347	neutral	None	None	None	None	I
N/G	0.1271	likely_benign	0.1397	benign	-0.182	Destabilizing	None	N	0.155	neutral	None	None	None	None	I
N/H	0.1153	likely_benign	0.1268	benign	-0.23	Destabilizing	0.295	N	0.309	neutral	N	0.512005829	None	None	I
N/I	0.2494	likely_benign	0.2945	benign	0.039	Stabilizing	0.295	N	0.395	neutral	N	0.462404065	None	None	I
N/K	0.2255	likely_benign	0.2557	benign	0.153	Stabilizing	0.055	N	0.215	neutral	N	0.486107306	None	None	I
N/L	0.2677	likely_benign	0.2974	benign	0.039	Stabilizing	0.072	N	0.437	neutral	None	None	None	None	I
N/M	0.3281	likely_benign	0.3504	ambiguous	0.165	Stabilizing	0.864	D	0.328	neutral	None	None	None	None	I
N/P	0.5461	ambiguous	0.5974	pathogenic	0.017	Stabilizing	0.136	N	0.406	neutral	None	None	None	None	I
N/Q	0.2149	likely_benign	0.2369	benign	-0.216	Destabilizing	0.072	N	0.295	neutral	None	None	None	None	I
N/R	0.2808	likely_benign	0.3213	benign	0.212	Stabilizing	0.072	N	0.301	neutral	None	None	None	None	I
N/S	0.0748	likely_benign	0.076	benign	0.014	Stabilizing	0.012	N	0.281	neutral	N	0.491859843	None	None	I
N/T	0.1117	likely_benign	0.1158	benign	0.06	Stabilizing	0.055	N	0.213	neutral	N	0.5053865	None	None	I
N/V	0.2236	likely_benign	0.2562	benign	0.017	Stabilizing	0.136	N	0.43	neutral	None	None	None	None	I
N/W	0.748	likely_pathogenic	0.8023	pathogenic	-0.837	Destabilizing	0.864	D	0.373	neutral	None	None	None	None	I
N/Y	0.1899	likely_benign	0.2236	benign	-0.509	Destabilizing	0.56	D	0.337	neutral	N	0.473506881	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.