TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9661	29206;29207;29208	chr2:178707586;178707585;178707584	chr2:179572313;179572312;179572311
N2AB	9344	28255;28256;28257	chr2:178707586;178707585;178707584	chr2:179572313;179572312;179572311
N2A	8417	25474;25475;25476	chr2:178707586;178707585;178707584	chr2:179572313;179572312;179572311
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-82
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1296
• 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
V/A	None	None	0.472	None	0.567	0.142	0.406531046227	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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
V/A	0.2998	likely_benign	0.2495	benign	-1.461	Destabilizing	0.472	N	0.567	neutral	None	None	None	None	N
V/C	0.8593	likely_pathogenic	0.8182	pathogenic	-0.924	Destabilizing	0.996	D	0.666	neutral	None	None	None	None	N
V/D	0.7264	likely_pathogenic	0.6036	pathogenic	-1.768	Destabilizing	0.953	D	0.711	prob.delet.	None	None	None	None	N
V/E	0.5237	ambiguous	0.3972	ambiguous	-1.524	Destabilizing	0.939	D	0.698	prob.neutral	None	None	None	None	N
V/F	0.2212	likely_benign	0.1957	benign	-0.729	Destabilizing	0.009	N	0.554	neutral	None	None	None	None	N
V/G	0.4534	ambiguous	0.3699	ambiguous	-2.021	Highly Destabilizing	0.815	D	0.711	prob.delet.	None	None	None	None	N
V/H	0.7572	likely_pathogenic	0.664	pathogenic	-1.905	Destabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
V/I	0.0793	likely_benign	0.0809	benign	0.101	Stabilizing	0.373	N	0.514	neutral	None	None	None	None	N
V/K	0.6993	likely_pathogenic	0.5566	ambiguous	-0.914	Destabilizing	0.742	D	0.693	prob.neutral	None	None	None	None	N
V/L	0.1961	likely_benign	0.1785	benign	0.101	Stabilizing	0.003	N	0.217	neutral	None	None	None	None	N
V/M	0.1701	likely_benign	0.1594	benign	-0.057	Destabilizing	0.164	N	0.418	neutral	None	None	None	None	N
V/N	0.4872	ambiguous	0.4366	ambiguous	-1.282	Destabilizing	0.953	D	0.717	prob.delet.	None	None	None	None	N
V/P	0.9882	likely_pathogenic	0.977	pathogenic	-0.391	Destabilizing	0.984	D	0.689	prob.neutral	None	None	None	None	N
V/Q	0.5121	ambiguous	0.4094	ambiguous	-1.042	Destabilizing	0.953	D	0.68	prob.neutral	None	None	None	None	N
V/R	0.6322	likely_pathogenic	0.467	ambiguous	-1.022	Destabilizing	0.91	D	0.717	prob.delet.	None	None	None	None	N
V/S	0.3133	likely_benign	0.277	benign	-1.931	Destabilizing	0.59	D	0.677	prob.neutral	None	None	None	None	N
V/T	0.2416	likely_benign	0.2192	benign	-1.53	Destabilizing	0.037	N	0.333	neutral	None	None	None	None	N
V/W	0.9051	likely_pathogenic	0.846	pathogenic	-1.271	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
V/Y	0.6734	likely_pathogenic	0.6098	pathogenic	-0.794	Destabilizing	0.835	D	0.721	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.