TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6221	18886;18887;18888	chr2:178729495;178729494;178729493	chr2:179594222;179594221;179594220
N2AB	5904	17935;17936;17937	chr2:178729495;178729494;178729493	chr2:179594222;179594221;179594220
N2A	4977	15154;15155;15156	chr2:178729495;178729494;178729493	chr2:179594222;179594221;179594220
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-46
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.5932
• 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
E/D	rs369544339	-1.044	0.92	D	0.405	0.115	0.24896430686	gnomAD-2.1.1	8.58E-05	None	None	None	None	I	None	4.14E-05	2.83E-05	None	1.06507E-03	0	None	3.27E-05	None	0	6.26E-05	2.80978E-04
E/D	rs369544339	-1.044	0.92	D	0.405	0.115	0.24896430686	gnomAD-3.1.2	1.05162E-04	None	None	None	None	I	None	2.41E-05	6.55E-05	0	2.59815E-03	0	None	0	0	5.88E-05	2.07039E-04	0
E/D	rs369544339	-1.044	0.92	D	0.405	0.115	0.24896430686	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/D	rs369544339	-1.044	0.92	D	0.405	0.115	0.24896430686	gnomAD-4.0.0	1.11549E-04	None	None	None	None	I	None	1.33305E-05	6.668E-05	None	1.6563E-03	0	None	0	0	9.15529E-05	4.39174E-05	2.24086E-04
E/G	rs1365356147	-1.39	0.959	N	0.552	0.355	0.527660502957	gnomAD-4.0.0	1.5917E-06	None	None	None	None	I	None	0	2.28739E-05	None	0	0	None	0	0	0	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
E/A	0.228	likely_benign	0.2373	benign	-1.282	Destabilizing	0.826	D	0.459	neutral	N	0.520514321	None	None	I
E/C	0.9005	likely_pathogenic	0.9149	pathogenic	-0.779	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
E/D	0.436	ambiguous	0.4155	ambiguous	-1.446	Destabilizing	0.92	D	0.405	neutral	D	0.529037804	None	None	I
E/F	0.8121	likely_pathogenic	0.8164	pathogenic	-0.845	Destabilizing	0.982	D	0.581	neutral	None	None	None	None	I
E/G	0.4572	ambiguous	0.4215	ambiguous	-1.677	Destabilizing	0.959	D	0.552	neutral	N	0.493912444	None	None	I
E/H	0.6035	likely_pathogenic	0.574	pathogenic	-1.056	Destabilizing	0.1	N	0.27	neutral	None	None	None	None	I
E/I	0.3727	ambiguous	0.4082	ambiguous	-0.176	Destabilizing	0.884	D	0.566	neutral	None	None	None	None	I
E/K	0.2338	likely_benign	0.1951	benign	-1.154	Destabilizing	0.852	D	0.431	neutral	N	0.508891818	None	None	I
E/L	0.4844	ambiguous	0.5254	ambiguous	-0.176	Destabilizing	0.02	N	0.429	neutral	None	None	None	None	I
E/M	0.4514	ambiguous	0.4769	ambiguous	0.449	Stabilizing	0.982	D	0.569	neutral	None	None	None	None	I
E/N	0.5581	ambiguous	0.5622	ambiguous	-1.5	Destabilizing	0.939	D	0.466	neutral	None	None	None	None	I
E/P	0.9848	likely_pathogenic	0.974	pathogenic	-0.526	Destabilizing	0.997	D	0.573	neutral	None	None	None	None	I
E/Q	0.1539	likely_benign	0.1545	benign	-1.342	Destabilizing	0.31	N	0.285	neutral	N	0.47941706	None	None	I
E/R	0.3685	ambiguous	0.3085	benign	-0.912	Destabilizing	0.939	D	0.465	neutral	None	None	None	None	I
E/S	0.3481	ambiguous	0.3528	ambiguous	-2.025	Highly Destabilizing	0.939	D	0.421	neutral	None	None	None	None	I
E/T	0.3223	likely_benign	0.3263	benign	-1.678	Destabilizing	0.969	D	0.482	neutral	None	None	None	None	I
E/V	0.2335	likely_benign	0.2511	benign	-0.526	Destabilizing	0.852	D	0.529	neutral	D	0.527480366	None	None	I
E/W	0.9448	likely_pathogenic	0.9326	pathogenic	-0.682	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	I
E/Y	0.778	likely_pathogenic	0.7656	pathogenic	-0.596	Destabilizing	0.982	D	0.569	neutral	None	None	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.