TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2633	8122;8123;8124	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155
N2AB	2633	8122;8123;8124	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155
N2A	2633	8122;8123;8124	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155
N2B	2587	7984;7985;7986	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155
Novex-1	2587	7984;7985;7986	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155
Novex-2	2587	7984;7985;7986	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155
Novex-3	2633	8122;8123;8124	chr2:178771430;178771429;178771428	chr2:179636157;179636156;179636155

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 13
• Structural Position: 23
• Q(SASA): 0.3675
• 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	0.999	N	0.628	0.391	0.232513804876	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85768E-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	0.612	likely_pathogenic	0.6042	pathogenic	-0.773	Destabilizing	0.999	D	0.628	neutral	N	0.342915591	None	None	N
E/C	0.9949	likely_pathogenic	0.9939	pathogenic	-0.33	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/D	0.6408	likely_pathogenic	0.6522	pathogenic	-1.093	Destabilizing	0.999	D	0.452	neutral	N	0.366799252	None	None	N
E/F	0.9869	likely_pathogenic	0.9853	pathogenic	-0.552	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/G	0.7573	likely_pathogenic	0.7509	pathogenic	-1.101	Destabilizing	1.0	D	0.675	prob.neutral	N	0.51320627	None	None	N
E/H	0.9711	likely_pathogenic	0.968	pathogenic	-0.87	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
E/I	0.8976	likely_pathogenic	0.8874	pathogenic	0.106	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.7471	likely_pathogenic	0.7127	pathogenic	-0.445	Destabilizing	0.999	D	0.599	neutral	N	0.322788735	None	None	N
E/L	0.9276	likely_pathogenic	0.9164	pathogenic	0.106	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.9385	likely_pathogenic	0.9311	pathogenic	0.565	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	N
E/N	0.8825	likely_pathogenic	0.8844	pathogenic	-0.81	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/P	0.9663	likely_pathogenic	0.9618	pathogenic	-0.166	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/Q	0.6101	likely_pathogenic	0.6005	pathogenic	-0.724	Destabilizing	1.0	D	0.624	neutral	N	0.418313911	None	None	N
E/R	0.8755	likely_pathogenic	0.851	pathogenic	-0.305	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/S	0.7769	likely_pathogenic	0.7843	pathogenic	-1.107	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/T	0.8772	likely_pathogenic	0.8714	pathogenic	-0.838	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/V	0.7867	likely_pathogenic	0.7634	pathogenic	-0.166	Destabilizing	1.0	D	0.72	prob.delet.	N	0.32429102	None	None	N
E/W	0.9976	likely_pathogenic	0.9971	pathogenic	-0.397	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/Y	0.9815	likely_pathogenic	0.9782	pathogenic	-0.311	Destabilizing	1.0	D	0.677	prob.neutral	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.