TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16019	48280;48281;48282	chr2:178616834;178616833;178616832	chr2:179481561;179481560;179481559
N2AB	14378	43357;43358;43359	chr2:178616834;178616833;178616832	chr2:179481561;179481560;179481559
N2A	13451	40576;40577;40578	chr2:178616834;178616833;178616832	chr2:179481561;179481560;179481559
N2B	6954	21085;21086;21087	chr2:178616834;178616833;178616832	chr2:179481561;179481560;179481559
Novex-1	7079	21460;21461;21462	chr2:178616834;178616833;178616832	chr2:179481561;179481560;179481559
Novex-2	7146	21661;21662;21663	chr2:178616834;178616833;178616832	chr2:179481561;179481560;179481559
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-109
• Domain position: 52
• Structural Position: 137
• Q(SASA): 0.1994
• 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
E/A	None	None	0.977	D	0.559	0.442	0.509820907775	gnomAD-4.0.0	3.18685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72413E-06	0	0
E/K	rs758399903	-1.281	0.992	N	0.517	0.291	0.45563089846	gnomAD-2.1.1	4.85E-05	None	None	None	None	N	None	0	2.9E-05	None	0	5.61E-05	None	2.28818E-04	None	0	2.69E-05	0
E/K	rs758399903	-1.281	0.992	N	0.517	0.291	0.45563089846	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	1.47E-05	2.07641E-04	0
E/K	rs758399903	-1.281	0.992	N	0.517	0.291	0.45563089846	gnomAD-4.0.0	2.29462E-05	None	None	None	None	N	None	1.33761E-05	1.66978E-05	None	0	2.23724E-05	None	0	0	1.27207E-05	1.97707E-04	1.60282E-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
E/A	0.2841	likely_benign	0.3143	benign	-0.439	Destabilizing	0.977	D	0.559	neutral	D	0.549141635	None	None	N
E/C	0.9073	likely_pathogenic	0.9165	pathogenic	-0.16	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/D	0.5171	ambiguous	0.5757	pathogenic	-1.525	Destabilizing	0.977	D	0.501	neutral	D	0.593252562	None	None	N
E/F	0.9062	likely_pathogenic	0.9112	pathogenic	0.191	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
E/G	0.4037	ambiguous	0.4428	ambiguous	-0.921	Destabilizing	0.993	D	0.715	prob.delet.	N	0.502298605	None	None	N
E/H	0.5949	likely_pathogenic	0.6395	pathogenic	-0.097	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/I	0.6555	likely_pathogenic	0.6735	pathogenic	0.914	Stabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
E/K	0.2191	likely_benign	0.26	benign	-0.678	Destabilizing	0.992	D	0.517	neutral	N	0.50668599	None	None	N
E/L	0.6841	likely_pathogenic	0.7054	pathogenic	0.914	Stabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
E/M	0.6404	likely_pathogenic	0.663	pathogenic	1.485	Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
E/N	0.5734	likely_pathogenic	0.6357	pathogenic	-1.261	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
E/P	0.985	likely_pathogenic	0.986	pathogenic	0.485	Stabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
E/Q	0.1653	likely_benign	0.1801	benign	-0.917	Destabilizing	0.77	D	0.309	neutral	N	0.506089358	None	None	N
E/R	0.378	ambiguous	0.4251	ambiguous	-0.599	Destabilizing	0.99	D	0.685	prob.neutral	None	None	None	None	N
E/S	0.3144	likely_benign	0.3515	ambiguous	-1.755	Destabilizing	0.983	D	0.573	neutral	None	None	None	None	N
E/T	0.4013	ambiguous	0.4321	ambiguous	-1.316	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	N
E/V	0.4346	ambiguous	0.4599	ambiguous	0.485	Stabilizing	0.997	D	0.782	deleterious	N	0.512590353	None	None	N
E/W	0.9672	likely_pathogenic	0.9699	pathogenic	0.171	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/Y	0.8209	likely_pathogenic	0.8409	pathogenic	0.431	Stabilizing	0.999	D	0.84	deleterious	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.