TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20743	62452;62453;62454	chr2:178589498;178589497;178589496	chr2:179454225;179454224;179454223
N2AB	19102	57529;57530;57531	chr2:178589498;178589497;178589496	chr2:179454225;179454224;179454223
N2A	18175	54748;54749;54750	chr2:178589498;178589497;178589496	chr2:179454225;179454224;179454223
N2B	11678	35257;35258;35259	chr2:178589498;178589497;178589496	chr2:179454225;179454224;179454223
Novex-1	11803	35632;35633;35634	chr2:178589498;178589497;178589496	chr2:179454225;179454224;179454223
Novex-2	11870	35833;35834;35835	chr2:178589498;178589497;178589496	chr2:179454225;179454224;179454223
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: Fn3-38
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0788
• 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	rs762990827	-3.047	0.999	D	0.657	0.7	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs762990827	-3.047	0.999	D	0.657	0.7	None	gnomAD-4.0.0	1.85975E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.5432E-06	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
V/A	0.9342	likely_pathogenic	0.9345	pathogenic	-2.553	Highly Destabilizing	0.999	D	0.657	neutral	D	0.544414819	None	None	N
V/C	0.9626	likely_pathogenic	0.9598	pathogenic	-1.796	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9994	pathogenic	-3.187	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/E	0.9984	likely_pathogenic	0.9975	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.612767811	None	None	N
V/F	0.967	likely_pathogenic	0.9748	pathogenic	-1.479	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/G	0.9638	likely_pathogenic	0.9572	pathogenic	-3.032	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.612767811	None	None	N
V/H	0.9996	likely_pathogenic	0.9994	pathogenic	-2.705	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.1758	likely_benign	0.1865	benign	-1.125	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
V/K	0.9988	likely_pathogenic	0.9983	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/L	0.8568	likely_pathogenic	0.8653	pathogenic	-1.125	Destabilizing	0.997	D	0.673	neutral	N	0.51386094	None	None	N
V/M	0.9231	likely_pathogenic	0.9363	pathogenic	-1.418	Destabilizing	1.0	D	0.797	deleterious	D	0.529526568	None	None	N
V/N	0.9983	likely_pathogenic	0.9974	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/P	0.9991	likely_pathogenic	0.9986	pathogenic	-1.592	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/Q	0.9978	likely_pathogenic	0.9967	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/R	0.9966	likely_pathogenic	0.9951	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/S	0.9889	likely_pathogenic	0.9857	pathogenic	-3.073	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/T	0.9642	likely_pathogenic	0.9577	pathogenic	-2.68	Highly Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9996	pathogenic	-1.807	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/Y	0.9976	likely_pathogenic	0.9977	pathogenic	-1.703	Destabilizing	1.0	D	0.83	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.