TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25063	75412;75413;75414	chr2:178570945;178570944;178570943	chr2:179435672;179435671;179435670
N2AB	23422	70489;70490;70491	chr2:178570945;178570944;178570943	chr2:179435672;179435671;179435670
N2A	22495	67708;67709;67710	chr2:178570945;178570944;178570943	chr2:179435672;179435671;179435670
N2B	15998	48217;48218;48219	chr2:178570945;178570944;178570943	chr2:179435672;179435671;179435670
Novex-1	16123	48592;48593;48594	chr2:178570945;178570944;178570943	chr2:179435672;179435671;179435670
Novex-2	16190	48793;48794;48795	chr2:178570945;178570944;178570943	chr2:179435672;179435671;179435670
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-70
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.2066
• 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
D/H	rs1707970781	None	0.602	N	0.329	0.259	0.190952846119	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85928E-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
D/A	0.1879	likely_benign	0.2172	benign	-0.215	Destabilizing	0.042	N	0.322	neutral	N	0.460510721	None	None	N
D/C	0.7254	likely_pathogenic	0.7585	pathogenic	-0.286	Destabilizing	0.958	D	0.4	neutral	None	None	None	None	N
D/E	0.107	likely_benign	0.1215	benign	-0.509	Destabilizing	None	N	0.098	neutral	N	0.414989075	None	None	N
D/F	0.7845	likely_pathogenic	0.8064	pathogenic	0.393	Stabilizing	0.497	N	0.413	neutral	None	None	None	None	N
D/G	0.1618	likely_benign	0.188	benign	-0.546	Destabilizing	0.175	N	0.337	neutral	N	0.470362355	None	None	N
D/H	0.3511	ambiguous	0.3854	ambiguous	0.429	Stabilizing	0.602	D	0.329	neutral	N	0.500087829	None	None	N
D/I	0.6132	likely_pathogenic	0.6385	pathogenic	0.656	Stabilizing	0.001	N	0.386	neutral	None	None	None	None	N
D/K	0.4195	ambiguous	0.464	ambiguous	-0.199	Destabilizing	0.002	N	0.185	neutral	None	None	None	None	N
D/L	0.539	ambiguous	0.5757	pathogenic	0.656	Stabilizing	0.02	N	0.372	neutral	None	None	None	None	N
D/M	0.7096	likely_pathogenic	0.7454	pathogenic	0.717	Stabilizing	0.497	N	0.394	neutral	None	None	None	None	N
D/N	0.1085	likely_benign	0.1184	benign	-0.735	Destabilizing	0.175	N	0.282	neutral	N	0.501586552	None	None	N
D/P	0.8828	likely_pathogenic	0.9007	pathogenic	0.391	Stabilizing	0.364	N	0.343	neutral	None	None	None	None	N
D/Q	0.3213	likely_benign	0.3662	ambiguous	-0.577	Destabilizing	0.124	N	0.245	neutral	None	None	None	None	N
D/R	0.5051	ambiguous	0.5419	ambiguous	0.172	Stabilizing	0.124	N	0.336	neutral	None	None	None	None	N
D/S	0.1197	likely_benign	0.1372	benign	-0.934	Destabilizing	0.055	N	0.262	neutral	None	None	None	None	N
D/T	0.2542	likely_benign	0.2854	benign	-0.654	Destabilizing	0.22	N	0.316	neutral	None	None	None	None	N
D/V	0.3924	ambiguous	0.4111	ambiguous	0.391	Stabilizing	0.015	N	0.362	neutral	N	0.494449936	None	None	N
D/W	0.9496	likely_pathogenic	0.9568	pathogenic	0.58	Stabilizing	0.958	D	0.441	neutral	None	None	None	None	N
D/Y	0.4481	ambiguous	0.4582	ambiguous	0.642	Stabilizing	0.602	D	0.415	neutral	N	0.516404076	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.