TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24031	72316;72317;72318	chr2:178574041;178574040;178574039	chr2:179438768;179438767;179438766
N2AB	22390	67393;67394;67395	chr2:178574041;178574040;178574039	chr2:179438768;179438767;179438766
N2A	21463	64612;64613;64614	chr2:178574041;178574040;178574039	chr2:179438768;179438767;179438766
N2B	14966	45121;45122;45123	chr2:178574041;178574040;178574039	chr2:179438768;179438767;179438766
Novex-1	15091	45496;45497;45498	chr2:178574041;178574040;178574039	chr2:179438768;179438767;179438766
Novex-2	15158	45697;45698;45699	chr2:178574041;178574040;178574039	chr2:179438768;179438767;179438766
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-131
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.6297
• 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/A	None	None	0.103	N	0.145	0.261	0.589635058153	gnomAD-4.0.0	3.18428E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71991E-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	0.217	likely_benign	0.229	benign	-1.587	Destabilizing	0.103	N	0.145	neutral	N	0.472813588	None	None	I
V/C	0.8744	likely_pathogenic	0.8662	pathogenic	-0.923	Destabilizing	0.076	N	0.297	neutral	None	None	None	None	I
V/D	0.7633	likely_pathogenic	0.7592	pathogenic	-1.677	Destabilizing	0.988	D	0.573	neutral	None	None	None	None	I
V/E	0.6949	likely_pathogenic	0.7068	pathogenic	-1.541	Destabilizing	0.984	D	0.505	neutral	N	0.511467977	None	None	I
V/F	0.4196	ambiguous	0.4431	ambiguous	-1.065	Destabilizing	0.976	D	0.48	neutral	None	None	None	None	I
V/G	0.3867	ambiguous	0.3842	ambiguous	-2.035	Highly Destabilizing	0.811	D	0.477	neutral	N	0.511641335	None	None	I
V/H	0.9256	likely_pathogenic	0.926	pathogenic	-1.732	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	I
V/I	0.116	likely_benign	0.1178	benign	-0.392	Destabilizing	0.702	D	0.379	neutral	None	None	None	None	I
V/K	0.7871	likely_pathogenic	0.7982	pathogenic	-1.174	Destabilizing	0.976	D	0.489	neutral	None	None	None	None	I
V/L	0.4032	ambiguous	0.4076	ambiguous	-0.392	Destabilizing	0.379	N	0.341	neutral	N	0.360893592	None	None	I
V/M	0.2671	likely_benign	0.2864	benign	-0.295	Destabilizing	0.64	D	0.313	neutral	N	0.414517433	None	None	I
V/N	0.72	likely_pathogenic	0.713	pathogenic	-1.228	Destabilizing	0.996	D	0.566	neutral	None	None	None	None	I
V/P	0.6737	likely_pathogenic	0.6655	pathogenic	-0.759	Destabilizing	0.988	D	0.54	neutral	None	None	None	None	I
V/Q	0.7805	likely_pathogenic	0.7803	pathogenic	-1.189	Destabilizing	0.988	D	0.524	neutral	None	None	None	None	I
V/R	0.7694	likely_pathogenic	0.7717	pathogenic	-0.963	Destabilizing	0.988	D	0.569	neutral	None	None	None	None	I
V/S	0.4966	ambiguous	0.4925	ambiguous	-1.804	Destabilizing	0.851	D	0.45	neutral	None	None	None	None	I
V/T	0.245	likely_benign	0.2459	benign	-1.53	Destabilizing	0.919	D	0.364	neutral	None	None	None	None	I
V/W	0.94	likely_pathogenic	0.9404	pathogenic	-1.458	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
V/Y	0.8418	likely_pathogenic	0.8428	pathogenic	-1.046	Destabilizing	0.988	D	0.466	neutral	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.