TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14773	44542;44543;44544	chr2:178629408;178629407;178629406	chr2:179494135;179494134;179494133
N2AB	13132	39619;39620;39621	chr2:178629408;178629407;178629406	chr2:179494135;179494134;179494133
N2A	12205	36838;36839;36840	chr2:178629408;178629407;178629406	chr2:179494135;179494134;179494133
N2B	5708	17347;17348;17349	chr2:178629408;178629407;178629406	chr2:179494135;179494134;179494133
Novex-1	5833	17722;17723;17724	chr2:178629408;178629407;178629406	chr2:179494135;179494134;179494133
Novex-2	5900	17923;17924;17925	chr2:178629408;178629407;178629406	chr2:179494135;179494134;179494133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-99
• Domain position: 9
• Structural Position: 13
• Q(SASA): 0.2235
• 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/I	rs2059498760	None	0.002	D	0.322	0.138	0.522717468363	gnomAD-4.0.0	1.59312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0281E-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
V/A	0.331	likely_benign	0.3865	ambiguous	-1.17	Destabilizing	0.007	N	0.344	neutral	D	0.559416857	None	None	N
V/C	0.8448	likely_pathogenic	0.8562	pathogenic	-0.812	Destabilizing	0.982	D	0.559	neutral	None	None	None	None	N
V/D	0.746	likely_pathogenic	0.7874	pathogenic	-0.688	Destabilizing	0.781	D	0.699	prob.neutral	D	0.722892208	None	None	N
V/E	0.5465	ambiguous	0.5768	pathogenic	-0.673	Destabilizing	0.826	D	0.632	neutral	None	None	None	None	N
V/F	0.4087	ambiguous	0.4614	ambiguous	-0.857	Destabilizing	0.638	D	0.583	neutral	D	0.721420955	None	None	N
V/G	0.5531	ambiguous	0.6006	pathogenic	-1.486	Destabilizing	0.638	D	0.622	neutral	D	0.68478078	None	None	N
V/H	0.8297	likely_pathogenic	0.8534	pathogenic	-0.987	Destabilizing	0.982	D	0.685	prob.neutral	None	None	None	None	N
V/I	0.0869	likely_benign	0.0892	benign	-0.408	Destabilizing	0.002	N	0.322	neutral	D	0.543553858	None	None	N
V/K	0.5172	ambiguous	0.5515	ambiguous	-0.904	Destabilizing	0.826	D	0.635	neutral	None	None	None	None	N
V/L	0.4333	ambiguous	0.4735	ambiguous	-0.408	Destabilizing	0.034	N	0.378	neutral	N	0.518625416	None	None	N
V/M	0.2128	likely_benign	0.2326	benign	-0.423	Destabilizing	0.7	D	0.491	neutral	None	None	None	None	N
V/N	0.5464	ambiguous	0.6331	pathogenic	-0.758	Destabilizing	0.935	D	0.715	prob.delet.	None	None	None	None	N
V/P	0.9861	likely_pathogenic	0.9885	pathogenic	-0.626	Destabilizing	0.826	D	0.647	neutral	None	None	None	None	N
V/Q	0.4924	ambiguous	0.5135	ambiguous	-0.853	Destabilizing	0.935	D	0.665	neutral	None	None	None	None	N
V/R	0.5164	ambiguous	0.523	ambiguous	-0.504	Destabilizing	0.826	D	0.717	prob.delet.	None	None	None	None	N
V/S	0.4665	ambiguous	0.5307	ambiguous	-1.297	Destabilizing	0.539	D	0.563	neutral	None	None	None	None	N
V/T	0.2657	likely_benign	0.3022	benign	-1.157	Destabilizing	0.399	N	0.415	neutral	None	None	None	None	N
V/W	0.9719	likely_pathogenic	0.9691	pathogenic	-1.052	Destabilizing	0.982	D	0.651	neutral	None	None	None	None	N
V/Y	0.8299	likely_pathogenic	0.8515	pathogenic	-0.721	Destabilizing	0.826	D	0.599	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.