TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31822	95689;95690;95691	chr2:178545646;178545645;178545644	chr2:179410373;179410372;179410371
N2AB	30181	90766;90767;90768	chr2:178545646;178545645;178545644	chr2:179410373;179410372;179410371
N2A	29254	87985;87986;87987	chr2:178545646;178545645;178545644	chr2:179410373;179410372;179410371
N2B	22757	68494;68495;68496	chr2:178545646;178545645;178545644	chr2:179410373;179410372;179410371
Novex-1	22882	68869;68870;68871	chr2:178545646;178545645;178545644	chr2:179410373;179410372;179410371
Novex-2	22949	69070;69071;69072	chr2:178545646;178545645;178545644	chr2:179410373;179410372;179410371
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-120
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4441
• 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	N	0.679	0.506	0.355658859761	gnomAD-4.0.0	4.77426E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29873E-05	0
E/D	rs1302716458	-0.634	0.117	N	0.201	0.024	0.158396225186	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs1302716458	-0.634	0.117	N	0.201	0.024	0.158396225186	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
E/K	rs986919717	None	0.977	N	0.607	0.336	0.282179105231	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85883E-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
E/A	0.2588	likely_benign	0.2466	benign	-0.678	Destabilizing	0.977	D	0.679	prob.neutral	N	0.517710798	None	None	N
E/C	0.8876	likely_pathogenic	0.8769	pathogenic	-0.258	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/D	0.0949	likely_benign	0.0924	benign	-0.902	Destabilizing	0.117	N	0.201	neutral	N	0.364962899	None	None	N
E/F	0.8551	likely_pathogenic	0.8408	pathogenic	-0.541	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/G	0.1729	likely_benign	0.1418	benign	-0.975	Destabilizing	0.993	D	0.717	prob.delet.	N	0.468071411	None	None	N
E/H	0.6301	likely_pathogenic	0.5885	pathogenic	-0.873	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/I	0.7007	likely_pathogenic	0.6828	pathogenic	0.108	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
E/K	0.355	ambiguous	0.3075	benign	-0.505	Destabilizing	0.977	D	0.607	neutral	N	0.494833938	None	None	N
E/L	0.6244	likely_pathogenic	0.5937	pathogenic	0.108	Stabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
E/M	0.638	likely_pathogenic	0.6229	pathogenic	0.544	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.2082	likely_benign	0.1884	benign	-0.744	Destabilizing	0.99	D	0.714	prob.delet.	None	None	None	None	N
E/P	0.8856	likely_pathogenic	0.8793	pathogenic	-0.133	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
E/Q	0.21	likely_benign	0.1966	benign	-0.662	Destabilizing	0.997	D	0.683	prob.neutral	N	0.501010549	None	None	N
E/R	0.4985	ambiguous	0.4613	ambiguous	-0.358	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/S	0.2183	likely_benign	0.2012	benign	-1.006	Destabilizing	0.983	D	0.648	neutral	None	None	None	None	N
E/T	0.2981	likely_benign	0.2762	benign	-0.775	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
E/V	0.4921	ambiguous	0.4726	ambiguous	-0.133	Destabilizing	0.997	D	0.766	deleterious	N	0.493587643	None	None	N
E/W	0.9407	likely_pathogenic	0.9306	pathogenic	-0.434	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/Y	0.6964	likely_pathogenic	0.6674	pathogenic	-0.343	Destabilizing	1.0	D	0.727	prob.delet.	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.