TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8799	26620;26621;26622	chr2:178714379;178714378;178714377	chr2:179579106;179579105;179579104
N2AB	8482	25669;25670;25671	chr2:178714379;178714378;178714377	chr2:179579106;179579105;179579104
N2A	7555	22888;22889;22890	chr2:178714379;178714378;178714377	chr2:179579106;179579105;179579104
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-73
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.1336
• 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/M	rs1560601919	None	0.295	N	0.537	0.214	0.389283895039	gnomAD-4.0.0	6.15807E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09545E-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	0.062	likely_benign	0.0671	benign	-2.409	Highly Destabilizing	None	N	0.121	neutral	N	0.440208098	None	None	N
V/C	0.6192	likely_pathogenic	0.6916	pathogenic	-2.331	Highly Destabilizing	0.356	N	0.579	neutral	None	None	None	None	N
V/D	0.555	ambiguous	0.6092	pathogenic	-3.092	Highly Destabilizing	0.072	N	0.593	neutral	None	None	None	None	N
V/E	0.5376	ambiguous	0.5751	pathogenic	-2.872	Highly Destabilizing	0.024	N	0.509	neutral	D	0.535016615	None	None	N
V/F	0.3416	ambiguous	0.4145	ambiguous	-1.39	Destabilizing	0.356	N	0.637	neutral	None	None	None	None	N
V/G	0.1412	likely_benign	0.1706	benign	-2.905	Highly Destabilizing	0.012	N	0.467	neutral	D	0.535016615	None	None	N
V/H	0.8074	likely_pathogenic	0.8559	pathogenic	-2.408	Highly Destabilizing	0.628	D	0.604	neutral	None	None	None	None	N
V/I	0.092	likely_benign	0.0989	benign	-1.012	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	N
V/K	0.7033	likely_pathogenic	0.7502	pathogenic	-1.863	Destabilizing	0.072	N	0.513	neutral	None	None	None	None	N
V/L	0.1775	likely_benign	0.2164	benign	-1.012	Destabilizing	0.005	N	0.319	neutral	D	0.522962768	None	None	N
V/M	0.1693	likely_benign	0.2015	benign	-1.441	Destabilizing	0.295	N	0.537	neutral	N	0.511632441	None	None	N
V/N	0.3986	ambiguous	0.4422	ambiguous	-2.263	Highly Destabilizing	0.072	N	0.607	neutral	None	None	None	None	N
V/P	0.3177	likely_benign	0.3087	benign	-1.456	Destabilizing	0.072	N	0.581	neutral	None	None	None	None	N
V/Q	0.6092	likely_pathogenic	0.6588	pathogenic	-2.123	Highly Destabilizing	0.356	N	0.639	neutral	None	None	None	None	N
V/R	0.6389	likely_pathogenic	0.687	pathogenic	-1.685	Destabilizing	0.072	N	0.645	neutral	None	None	None	None	N
V/S	0.1374	likely_benign	0.1603	benign	-2.86	Highly Destabilizing	None	N	0.354	neutral	None	None	None	None	N
V/T	0.1066	likely_benign	0.1025	benign	-2.504	Highly Destabilizing	None	N	0.131	neutral	None	None	None	None	N
V/W	0.8799	likely_pathogenic	0.9265	pathogenic	-1.763	Destabilizing	0.864	D	0.577	neutral	None	None	None	None	N
V/Y	0.7419	likely_pathogenic	0.8115	pathogenic	-1.498	Destabilizing	0.356	N	0.625	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.