TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8561	25906;25907;25908	chr2:178715733;178715732;178715731	chr2:179580460;179580459;179580458
N2AB	8244	24955;24956;24957	chr2:178715733;178715732;178715731	chr2:179580460;179580459;179580458
N2A	7317	22174;22175;22176	chr2:178715733;178715732;178715731	chr2:179580460;179580459;179580458
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-71
• Domain position: 13
• Structural Position: 17
• Q(SASA): 0.2011
• 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/L	None	None	0.024	N	0.466	0.285	0.529110813561	gnomAD-4.0.0	6.92609E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.07438E-07	0	0
V/M	None	None	0.172	N	0.423	0.337	0.549249573952	gnomAD-4.0.0	6.23348E-06	None	None	None	None	I	None	3.01132E-05	0	None	0	0	None	0	0	7.2595E-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	0.2535	likely_benign	0.2862	benign	-1.785	Destabilizing	0.312	N	0.496	neutral	N	0.510897547	None	None	I
V/C	0.7811	likely_pathogenic	0.8356	pathogenic	-1.269	Destabilizing	0.996	D	0.565	neutral	None	None	None	None	I
V/D	0.7663	likely_pathogenic	0.8148	pathogenic	-1.917	Destabilizing	0.981	D	0.674	neutral	None	None	None	None	I
V/E	0.5083	ambiguous	0.5906	pathogenic	-1.819	Destabilizing	0.862	D	0.609	neutral	N	0.518558201	None	None	I
V/F	0.2571	likely_benign	0.3135	benign	-1.122	Destabilizing	0.95	D	0.623	neutral	None	None	None	None	I
V/G	0.3904	ambiguous	0.4391	ambiguous	-2.206	Highly Destabilizing	0.022	N	0.422	neutral	N	0.509417169	None	None	I
V/H	0.7334	likely_pathogenic	0.8146	pathogenic	-1.818	Destabilizing	0.997	D	0.637	neutral	None	None	None	None	I
V/I	0.0875	likely_benign	0.0927	benign	-0.679	Destabilizing	0.085	N	0.487	neutral	None	None	None	None	I
V/K	0.5259	ambiguous	0.6334	pathogenic	-1.635	Destabilizing	0.899	D	0.611	neutral	None	None	None	None	I
V/L	0.1675	likely_benign	0.251	benign	-0.679	Destabilizing	0.024	N	0.466	neutral	N	0.490499538	None	None	I
V/M	0.163	likely_benign	0.2009	benign	-0.59	Destabilizing	0.172	N	0.423	neutral	N	0.515911629	None	None	I
V/N	0.6437	likely_pathogenic	0.7235	pathogenic	-1.613	Destabilizing	0.728	D	0.676	prob.neutral	None	None	None	None	I
V/P	0.9227	likely_pathogenic	0.9503	pathogenic	-1.016	Destabilizing	0.891	D	0.618	neutral	None	None	None	None	I
V/Q	0.4219	ambiguous	0.5381	ambiguous	-1.643	Destabilizing	0.927	D	0.613	neutral	None	None	None	None	I
V/R	0.4518	ambiguous	0.5769	pathogenic	-1.223	Destabilizing	0.95	D	0.675	prob.neutral	None	None	None	None	I
V/S	0.4024	ambiguous	0.47	ambiguous	-2.188	Highly Destabilizing	0.911	D	0.595	neutral	None	None	None	None	I
V/T	0.2866	likely_benign	0.3213	benign	-1.973	Destabilizing	0.54	D	0.549	neutral	None	None	None	None	I
V/W	0.8596	likely_pathogenic	0.9206	pathogenic	-1.481	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
V/Y	0.7051	likely_pathogenic	0.7843	pathogenic	-1.151	Destabilizing	0.975	D	0.603	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.