TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24197	72814;72815;72816	chr2:178573543;178573542;178573541	chr2:179438270;179438269;179438268
N2AB	22556	67891;67892;67893	chr2:178573543;178573542;178573541	chr2:179438270;179438269;179438268
N2A	21629	65110;65111;65112	chr2:178573543;178573542;178573541	chr2:179438270;179438269;179438268
N2B	15132	45619;45620;45621	chr2:178573543;178573542;178573541	chr2:179438270;179438269;179438268
Novex-1	15257	45994;45995;45996	chr2:178573543;178573542;178573541	chr2:179438270;179438269;179438268
Novex-2	15324	46195;46196;46197	chr2:178573543;178573542;178573541	chr2:179438270;179438269;179438268
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: Fn3-63
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0805
• 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	None	None	0.046	N	0.281	0.267	0.603037435086	gnomAD-4.0.0	3.90683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.2244E-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	0.8061	likely_pathogenic	0.8731	pathogenic	-2.726	Highly Destabilizing	0.939	D	0.583	neutral	D	0.574039963	None	None	N
V/C	0.9405	likely_pathogenic	0.9639	pathogenic	-2.211	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
V/D	0.9975	likely_pathogenic	0.9983	pathogenic	-3.76	Highly Destabilizing	0.997	D	0.901	deleterious	D	0.654557448	None	None	N
V/E	0.9937	likely_pathogenic	0.9949	pathogenic	-3.466	Highly Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
V/F	0.906	likely_pathogenic	0.948	pathogenic	-1.671	Destabilizing	0.982	D	0.806	deleterious	D	0.574039963	None	None	N
V/G	0.8888	likely_pathogenic	0.9248	pathogenic	-3.268	Highly Destabilizing	0.997	D	0.901	deleterious	D	0.654557448	None	None	N
V/H	0.9983	likely_pathogenic	0.999	pathogenic	-3.014	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
V/I	0.0895	likely_benign	0.1076	benign	-1.127	Destabilizing	0.046	N	0.281	neutral	N	0.518306309	None	None	N
V/K	0.9963	likely_pathogenic	0.9967	pathogenic	-2.475	Highly Destabilizing	0.993	D	0.891	deleterious	None	None	None	None	N
V/L	0.6355	likely_pathogenic	0.7602	pathogenic	-1.127	Destabilizing	0.76	D	0.49	neutral	D	0.531306859	None	None	N
V/M	0.7317	likely_pathogenic	0.8393	pathogenic	-1.32	Destabilizing	0.986	D	0.696	prob.neutral	None	None	None	None	N
V/N	0.9908	likely_pathogenic	0.9938	pathogenic	-3.12	Highly Destabilizing	0.998	D	0.908	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9965	pathogenic	-1.647	Destabilizing	0.998	D	0.894	deleterious	None	None	None	None	N
V/Q	0.9933	likely_pathogenic	0.9954	pathogenic	-2.832	Highly Destabilizing	0.998	D	0.904	deleterious	None	None	None	None	N
V/R	0.9924	likely_pathogenic	0.9936	pathogenic	-2.369	Highly Destabilizing	0.998	D	0.912	deleterious	None	None	None	None	N
V/S	0.9521	likely_pathogenic	0.9706	pathogenic	-3.587	Highly Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
V/T	0.8923	likely_pathogenic	0.9156	pathogenic	-3.157	Highly Destabilizing	0.953	D	0.663	neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9994	pathogenic	-2.205	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
V/Y	0.9918	likely_pathogenic	0.9958	pathogenic	-1.963	Destabilizing	0.998	D	0.809	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.