TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14197	42814;42815;42816	chr2:178633910;178633909;178633908	chr2:179498637;179498636;179498635
N2AB	12556	37891;37892;37893	chr2:178633910;178633909;178633908	chr2:179498637;179498636;179498635
N2A	11629	35110;35111;35112	chr2:178633910;178633909;178633908	chr2:179498637;179498636;179498635
N2B	5132	15619;15620;15621	chr2:178633910;178633909;178633908	chr2:179498637;179498636;179498635
Novex-1	5257	15994;15995;15996	chr2:178633910;178633909;178633908	chr2:179498637;179498636;179498635
Novex-2	5324	16195;16196;16197	chr2:178633910;178633909;178633908	chr2:179498637;179498636;179498635
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-92
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.2856
• 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
K/N	None	None	0.003	D	0.268	0.088	0.165133752707	gnomAD-4.0.0	6.8435E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99625E-07	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
K/A	0.5528	ambiguous	0.5296	ambiguous	-1.046	Destabilizing	0.345	N	0.473	neutral	None	None	None	None	N
K/C	0.6017	likely_pathogenic	0.6318	pathogenic	-1.246	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
K/D	0.8687	likely_pathogenic	0.8628	pathogenic	-0.803	Destabilizing	0.39	N	0.546	neutral	None	None	None	None	N
K/E	0.3224	likely_benign	0.2919	benign	-0.613	Destabilizing	0.491	N	0.537	neutral	N	0.509723219	None	None	N
K/F	0.7504	likely_pathogenic	0.7405	pathogenic	-0.563	Destabilizing	0.901	D	0.661	neutral	None	None	None	None	N
K/G	0.7709	likely_pathogenic	0.7591	pathogenic	-1.472	Destabilizing	0.39	N	0.598	neutral	None	None	None	None	N
K/H	0.2646	likely_benign	0.2779	benign	-1.708	Destabilizing	0.901	D	0.598	neutral	None	None	None	None	N
K/I	0.2592	likely_benign	0.2459	benign	0.103	Stabilizing	0.013	N	0.494	neutral	N	0.48678288	None	None	N
K/L	0.395	ambiguous	0.383	ambiguous	0.103	Stabilizing	0.209	N	0.497	neutral	None	None	None	None	N
K/M	0.2378	likely_benign	0.2234	benign	-0.118	Destabilizing	0.901	D	0.605	neutral	None	None	None	None	N
K/N	0.6145	likely_pathogenic	0.569	pathogenic	-1.119	Destabilizing	0.003	N	0.268	neutral	D	0.536256031	None	None	N
K/P	0.9902	likely_pathogenic	0.9918	pathogenic	-0.253	Destabilizing	0.965	D	0.609	neutral	None	None	None	None	N
K/Q	0.1543	likely_benign	0.1454	benign	-1.072	Destabilizing	0.772	D	0.567	neutral	N	0.507958615	None	None	N
K/R	0.0845	likely_benign	0.0889	benign	-0.881	Destabilizing	0.491	N	0.473	neutral	N	0.477044254	None	None	N
K/S	0.5694	likely_pathogenic	0.5483	ambiguous	-1.808	Destabilizing	0.209	N	0.515	neutral	None	None	None	None	N
K/T	0.1714	likely_benign	0.16	benign	-1.383	Destabilizing	0.013	N	0.3	neutral	N	0.446955243	None	None	N
K/V	0.2864	likely_benign	0.2826	benign	-0.253	Destabilizing	0.007	N	0.466	neutral	None	None	None	None	N
K/W	0.7509	likely_pathogenic	0.7941	pathogenic	-0.448	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
K/Y	0.5769	likely_pathogenic	0.5888	pathogenic	-0.118	Destabilizing	0.965	D	0.633	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.