TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28216	84871;84872;84873	chr2:178561486;178561485;178561484	chr2:179426213;179426212;179426211
N2AB	26575	79948;79949;79950	chr2:178561486;178561485;178561484	chr2:179426213;179426212;179426211
N2A	25648	77167;77168;77169	chr2:178561486;178561485;178561484	chr2:179426213;179426212;179426211
N2B	19151	57676;57677;57678	chr2:178561486;178561485;178561484	chr2:179426213;179426212;179426211
Novex-1	19276	58051;58052;58053	chr2:178561486;178561485;178561484	chr2:179426213;179426212;179426211
Novex-2	19343	58252;58253;58254	chr2:178561486;178561485;178561484	chr2:179426213;179426212;179426211
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: Fn3-93
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.149
• 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	None	None	0.989	N	0.661	0.374	0.628255493996	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4493	ambiguous	0.4646	ambiguous	-1.915	Destabilizing	0.989	D	0.661	neutral	N	0.489761766	None	None	N
V/C	0.8529	likely_pathogenic	0.8627	pathogenic	-1.438	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
V/D	0.9374	likely_pathogenic	0.9389	pathogenic	-2.088	Highly Destabilizing	0.999	D	0.821	deleterious	N	0.490672171	None	None	N
V/E	0.8823	likely_pathogenic	0.8824	pathogenic	-1.909	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/F	0.3864	ambiguous	0.3931	ambiguous	-1.186	Destabilizing	0.997	D	0.733	prob.delet.	N	0.490263642	None	None	N
V/G	0.6755	likely_pathogenic	0.6845	pathogenic	-2.42	Highly Destabilizing	0.998	D	0.823	deleterious	N	0.51217024	None	None	N
V/H	0.9456	likely_pathogenic	0.9478	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/I	0.0875	likely_benign	0.0864	benign	-0.537	Destabilizing	0.948	D	0.567	neutral	N	0.47444281	None	None	N
V/K	0.9262	likely_pathogenic	0.9243	pathogenic	-1.609	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/L	0.3541	ambiguous	0.3637	ambiguous	-0.537	Destabilizing	0.948	D	0.467	neutral	N	0.500335758	None	None	N
V/M	0.3444	ambiguous	0.3421	ambiguous	-0.524	Destabilizing	0.914	D	0.372	neutral	None	None	None	None	N
V/N	0.8527	likely_pathogenic	0.8503	pathogenic	-1.765	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/P	0.9576	likely_pathogenic	0.961	pathogenic	-0.966	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/Q	0.8791	likely_pathogenic	0.879	pathogenic	-1.668	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/R	0.8997	likely_pathogenic	0.9009	pathogenic	-1.386	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/S	0.7026	likely_pathogenic	0.7074	pathogenic	-2.41	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
V/T	0.5838	likely_pathogenic	0.5754	pathogenic	-2.078	Highly Destabilizing	0.996	D	0.631	neutral	None	None	None	None	N
V/W	0.9666	likely_pathogenic	0.9704	pathogenic	-1.573	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/Y	0.85	likely_pathogenic	0.8576	pathogenic	-1.204	Destabilizing	1.0	D	0.717	prob.delet.	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.