TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18336	55231;55232;55233	chr2:178602396;178602395;178602394	chr2:179467123;179467122;179467121
N2AB	16695	50308;50309;50310	chr2:178602396;178602395;178602394	chr2:179467123;179467122;179467121
N2A	15768	47527;47528;47529	chr2:178602396;178602395;178602394	chr2:179467123;179467122;179467121
N2B	9271	28036;28037;28038	chr2:178602396;178602395;178602394	chr2:179467123;179467122;179467121
Novex-1	9396	28411;28412;28413	chr2:178602396;178602395;178602394	chr2:179467123;179467122;179467121
Novex-2	9463	28612;28613;28614	chr2:178602396;178602395;178602394	chr2:179467123;179467122;179467121
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: Fn3-21
• Domain position: 65
• Structural Position: 93
• Q(SASA): 0.1305
• 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/E	None	None	0.997	D	0.879	0.632	0.813960563265	gnomAD-4.0.0	1.59327E-06	None	None	None	None	N	None	5.66958E-05	0	None	0	0	None	0	0	0	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	0.639	likely_pathogenic	0.5063	ambiguous	-1.883	Destabilizing	0.939	D	0.68	prob.neutral	N	0.489190913	None	None	N
V/C	0.8871	likely_pathogenic	0.8585	pathogenic	-1.523	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
V/D	0.9843	likely_pathogenic	0.9789	pathogenic	-2.067	Highly Destabilizing	0.998	D	0.878	deleterious	None	None	None	None	N
V/E	0.9481	likely_pathogenic	0.9359	pathogenic	-1.848	Destabilizing	0.997	D	0.879	deleterious	D	0.527311981	None	None	N
V/F	0.4716	ambiguous	0.3809	ambiguous	-1.127	Destabilizing	0.986	D	0.833	deleterious	None	None	None	None	N
V/G	0.8786	likely_pathogenic	0.8149	pathogenic	-2.415	Highly Destabilizing	0.991	D	0.885	deleterious	D	0.522539041	None	None	N
V/H	0.9723	likely_pathogenic	0.9614	pathogenic	-2.046	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
V/I	0.0851	likely_benign	0.0818	benign	-0.41	Destabilizing	0.06	N	0.228	neutral	None	None	None	None	N
V/K	0.9599	likely_pathogenic	0.9507	pathogenic	-1.587	Destabilizing	0.993	D	0.876	deleterious	None	None	None	None	N
V/L	0.4266	ambiguous	0.3459	ambiguous	-0.41	Destabilizing	0.76	D	0.425	neutral	N	0.518921519	None	None	N
V/M	0.4455	ambiguous	0.3623	ambiguous	-0.508	Destabilizing	0.76	D	0.535	neutral	N	0.510675756	None	None	N
V/N	0.9511	likely_pathogenic	0.9383	pathogenic	-1.883	Destabilizing	0.998	D	0.886	deleterious	None	None	None	None	N
V/P	0.9682	likely_pathogenic	0.9609	pathogenic	-0.873	Destabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
V/Q	0.9332	likely_pathogenic	0.914	pathogenic	-1.696	Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
V/R	0.9383	likely_pathogenic	0.9261	pathogenic	-1.507	Destabilizing	0.993	D	0.882	deleterious	None	None	None	None	N
V/S	0.8534	likely_pathogenic	0.7846	pathogenic	-2.545	Highly Destabilizing	0.993	D	0.852	deleterious	None	None	None	None	N
V/T	0.7891	likely_pathogenic	0.6992	pathogenic	-2.159	Highly Destabilizing	0.953	D	0.693	prob.neutral	None	None	None	None	N
V/W	0.9759	likely_pathogenic	0.9688	pathogenic	-1.515	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/Y	0.8987	likely_pathogenic	0.8635	pathogenic	-1.131	Destabilizing	0.998	D	0.815	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.