TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16093	48502;48503;48504	chr2:178616514;178616513;178616512	chr2:179481241;179481240;179481239
N2AB	14452	43579;43580;43581	chr2:178616514;178616513;178616512	chr2:179481241;179481240;179481239
N2A	13525	40798;40799;40800	chr2:178616514;178616513;178616512	chr2:179481241;179481240;179481239
N2B	7028	21307;21308;21309	chr2:178616514;178616513;178616512	chr2:179481241;179481240;179481239
Novex-1	7153	21682;21683;21684	chr2:178616514;178616513;178616512	chr2:179481241;179481240;179481239
Novex-2	7220	21883;21884;21885	chr2:178616514;178616513;178616512	chr2:179481241;179481240;179481239
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: Fn3-4
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1416
• 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/Q	rs1320775896	-1.362	0.01	N	0.357	0.145	0.134241683229	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
E/Q	rs1320775896	-1.362	0.01	N	0.357	0.145	0.134241683229	gnomAD-4.0.0	1.59429E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86457E-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	0.6597	likely_pathogenic	0.7219	pathogenic	-1.53	Destabilizing	0.41	N	0.665	neutral	D	0.657097924	None	None	N
E/C	0.9578	likely_pathogenic	0.9712	pathogenic	-0.88	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	N
E/D	0.4933	ambiguous	0.604	pathogenic	-1.692	Destabilizing	0.581	D	0.631	neutral	N	0.507805677	None	None	N
E/F	0.9271	likely_pathogenic	0.9538	pathogenic	-1.099	Destabilizing	0.993	D	0.823	deleterious	None	None	None	None	N
E/G	0.6976	likely_pathogenic	0.7634	pathogenic	-1.95	Destabilizing	0.83	D	0.754	deleterious	D	0.682270609	None	None	N
E/H	0.8823	likely_pathogenic	0.9163	pathogenic	-1.154	Destabilizing	0.961	D	0.838	deleterious	None	None	None	None	N
E/I	0.8453	likely_pathogenic	0.8882	pathogenic	-0.324	Destabilizing	0.929	D	0.825	deleterious	None	None	None	None	N
E/K	0.7317	likely_pathogenic	0.7788	pathogenic	-1.664	Destabilizing	0.41	N	0.651	neutral	D	0.638051635	None	None	N
E/L	0.7902	likely_pathogenic	0.8647	pathogenic	-0.324	Destabilizing	0.866	D	0.794	deleterious	None	None	None	None	N
E/M	0.7789	likely_pathogenic	0.8389	pathogenic	0.434	Stabilizing	0.98	D	0.818	deleterious	None	None	None	None	N
E/N	0.809	likely_pathogenic	0.8851	pathogenic	-1.923	Destabilizing	0.866	D	0.817	deleterious	None	None	None	None	N
E/P	0.999	likely_pathogenic	0.9991	pathogenic	-0.711	Destabilizing	0.929	D	0.804	deleterious	None	None	None	None	N
E/Q	0.3678	ambiguous	0.398	ambiguous	-1.612	Destabilizing	0.01	N	0.357	neutral	N	0.480700739	None	None	N
E/R	0.8383	likely_pathogenic	0.8717	pathogenic	-1.464	Destabilizing	0.764	D	0.818	deleterious	None	None	None	None	N
E/S	0.6367	likely_pathogenic	0.7284	pathogenic	-2.585	Highly Destabilizing	0.48	N	0.7	prob.neutral	None	None	None	None	N
E/T	0.761	likely_pathogenic	0.8281	pathogenic	-2.196	Highly Destabilizing	0.866	D	0.778	deleterious	None	None	None	None	N
E/V	0.714	likely_pathogenic	0.7753	pathogenic	-0.711	Destabilizing	0.83	D	0.779	deleterious	D	0.635618085	None	None	N
E/W	0.9673	likely_pathogenic	0.9789	pathogenic	-1.144	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
E/Y	0.8877	likely_pathogenic	0.9315	pathogenic	-0.925	Destabilizing	0.929	D	0.819	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.