TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26071	78436;78437;78438	chr2:178567921;178567920;178567919	chr2:179432648;179432647;179432646
N2AB	24430	73513;73514;73515	chr2:178567921;178567920;178567919	chr2:179432648;179432647;179432646
N2A	23503	70732;70733;70734	chr2:178567921;178567920;178567919	chr2:179432648;179432647;179432646
N2B	17006	51241;51242;51243	chr2:178567921;178567920;178567919	chr2:179432648;179432647;179432646
Novex-1	17131	51616;51617;51618	chr2:178567921;178567920;178567919	chr2:179432648;179432647;179432646
Novex-2	17198	51817;51818;51819	chr2:178567921;178567920;178567919	chr2:179432648;179432647;179432646
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-77
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5083
• Predicted PPI site: I

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	rs1706545322	None	0.997	N	0.477	0.29	0.474406357249	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
V/I	rs1706545322	None	0.997	N	0.477	0.29	0.474406357249	gnomAD-4.0.0	5.12608E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	5.36035E-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	0.1776	likely_benign	0.2325	benign	-0.439	Destabilizing	0.999	D	0.568	neutral	N	0.39168814	None	None	I
V/C	0.8142	likely_pathogenic	0.8284	pathogenic	-0.789	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
V/D	0.9746	likely_pathogenic	0.9849	pathogenic	-0.336	Destabilizing	1.0	D	0.831	deleterious	N	0.478850749	None	None	I
V/E	0.9394	likely_pathogenic	0.9612	pathogenic	-0.455	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
V/F	0.6192	likely_pathogenic	0.67	pathogenic	-0.686	Destabilizing	1.0	D	0.78	deleterious	D	0.522503329	None	None	I
V/G	0.6546	likely_pathogenic	0.7307	pathogenic	-0.537	Destabilizing	1.0	D	0.791	deleterious	N	0.473468698	None	None	I
V/H	0.963	likely_pathogenic	0.9715	pathogenic	-0.01	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
V/I	0.1624	likely_benign	0.1693	benign	-0.334	Destabilizing	0.997	D	0.477	neutral	N	0.484291657	None	None	I
V/K	0.9465	likely_pathogenic	0.9614	pathogenic	-0.438	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
V/L	0.7508	likely_pathogenic	0.7858	pathogenic	-0.334	Destabilizing	0.997	D	0.56	neutral	N	0.5112089	None	None	I
V/M	0.5225	ambiguous	0.601	pathogenic	-0.479	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
V/N	0.8975	likely_pathogenic	0.9336	pathogenic	-0.265	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
V/P	0.9624	likely_pathogenic	0.9712	pathogenic	-0.337	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
V/Q	0.8884	likely_pathogenic	0.9263	pathogenic	-0.511	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
V/R	0.8739	likely_pathogenic	0.907	pathogenic	0.11	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
V/S	0.4408	ambiguous	0.5339	ambiguous	-0.608	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
V/T	0.3953	ambiguous	0.4543	ambiguous	-0.628	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
V/W	0.9871	likely_pathogenic	0.9893	pathogenic	-0.731	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
V/Y	0.9525	likely_pathogenic	0.9615	pathogenic	-0.454	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I

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.