TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14480	43663;43664;43665	chr2:178632568;178632567;178632566	chr2:179497295;179497294;179497293
N2AB	12839	38740;38741;38742	chr2:178632568;178632567;178632566	chr2:179497295;179497294;179497293
N2A	11912	35959;35960;35961	chr2:178632568;178632567;178632566	chr2:179497295;179497294;179497293
N2B	5415	16468;16469;16470	chr2:178632568;178632567;178632566	chr2:179497295;179497294;179497293
Novex-1	5540	16843;16844;16845	chr2:178632568;178632567;178632566	chr2:179497295;179497294;179497293
Novex-2	5607	17044;17045;17046	chr2:178632568;178632567;178632566	chr2:179497295;179497294;179497293
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-95
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.405
• 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	0.707	0.405	0.508934680445	gnomAD-4.0.0	6.84385E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99624E-07	0	0
E/G	rs1449008181	-1.594	1.0	D	0.795	0.504	0.64458063076	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/G	rs1449008181	-1.594	1.0	D	0.795	0.504	0.64458063076	gnomAD-4.0.0	2.05315E-06	None	None	None	None	N	None	0	2.23694E-05	None	0	0	None	0	0	8.99624E-07	0	1.65761E-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	0.3452	ambiguous	0.305	benign	-1.172	Destabilizing	0.999	D	0.707	prob.neutral	N	0.510755985	None	None	N
E/C	0.9484	likely_pathogenic	0.9311	pathogenic	-0.834	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/D	0.669	likely_pathogenic	0.5861	pathogenic	-1.561	Destabilizing	0.999	D	0.539	neutral	N	0.510642928	None	None	N
E/F	0.8924	likely_pathogenic	0.8589	pathogenic	-0.772	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/G	0.6217	likely_pathogenic	0.5729	pathogenic	-1.6	Destabilizing	1.0	D	0.795	deleterious	D	0.618071929	None	None	N
E/H	0.7558	likely_pathogenic	0.6813	pathogenic	-1.151	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/I	0.4469	ambiguous	0.3974	ambiguous	0.037	Stabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
E/K	0.2985	likely_benign	0.2411	benign	-1.605	Destabilizing	0.999	D	0.621	neutral	N	0.503151226	None	None	N
E/L	0.6406	likely_pathogenic	0.5651	pathogenic	0.037	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/M	0.5966	likely_pathogenic	0.5261	ambiguous	0.739	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
E/N	0.8007	likely_pathogenic	0.7402	pathogenic	-1.892	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/P	0.9937	likely_pathogenic	0.9912	pathogenic	-0.347	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/Q	0.2157	likely_benign	0.1896	benign	-1.587	Destabilizing	1.0	D	0.683	prob.neutral	N	0.50570175	None	None	N
E/R	0.4658	ambiguous	0.3876	ambiguous	-1.447	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/S	0.5224	ambiguous	0.4659	ambiguous	-2.469	Highly Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
E/T	0.4882	ambiguous	0.4203	ambiguous	-2.093	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/V	0.2819	likely_benign	0.244	benign	-0.347	Destabilizing	1.0	D	0.843	deleterious	N	0.468540224	None	None	N
E/W	0.9661	likely_pathogenic	0.9497	pathogenic	-0.824	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Y	0.8685	likely_pathogenic	0.8242	pathogenic	-0.632	Destabilizing	1.0	D	0.865	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.