TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35421	106486;106487;106488	chr2:178530354;178530353;178530352	chr2:179395081;179395080;179395079
N2AB	33780	101563;101564;101565	chr2:178530354;178530353;178530352	chr2:179395081;179395080;179395079
N2A	32853	98782;98783;98784	chr2:178530354;178530353;178530352	chr2:179395081;179395080;179395079
N2B	26356	79291;79292;79293	chr2:178530354;178530353;178530352	chr2:179395081;179395080;179395079
Novex-1	26481	79666;79667;79668	chr2:178530354;178530353;178530352	chr2:179395081;179395080;179395079
Novex-2	26548	79867;79868;79869	chr2:178530354;178530353;178530352	chr2:179395081;179395080;179395079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-166
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3346
• 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	0.002	N	0.135	0.09	0.375861065471	gnomAD-4.0.0	1.59093E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.1261	likely_benign	0.1159	benign	-0.572	Destabilizing	0.393	N	0.288	neutral	N	0.500043049	None	None	I
V/C	0.7544	likely_pathogenic	0.7234	pathogenic	-0.793	Destabilizing	0.994	D	0.375	neutral	None	None	None	None	I
V/D	0.2272	likely_benign	0.215	benign	-0.351	Destabilizing	0.51	D	0.335	neutral	None	None	None	None	I
V/E	0.1568	likely_benign	0.1468	benign	-0.423	Destabilizing	0.005	N	0.238	neutral	N	0.477088831	None	None	I
V/F	0.1525	likely_benign	0.1505	benign	-0.592	Destabilizing	0.879	D	0.426	neutral	None	None	None	None	I
V/G	0.1887	likely_benign	0.1797	benign	-0.742	Destabilizing	0.761	D	0.375	neutral	N	0.518764882	None	None	I
V/H	0.4695	ambiguous	0.4474	ambiguous	-0.154	Destabilizing	0.982	D	0.383	neutral	None	None	None	None	I
V/I	0.0826	likely_benign	0.0796	benign	-0.252	Destabilizing	0.245	N	0.293	neutral	N	0.492002355	None	None	I
V/K	0.2165	likely_benign	0.2051	benign	-0.578	Destabilizing	0.51	D	0.317	neutral	None	None	None	None	I
V/L	0.1664	likely_benign	0.1551	benign	-0.252	Destabilizing	0.002	N	0.135	neutral	N	0.509433323	None	None	I
V/M	0.1247	likely_benign	0.1194	benign	-0.494	Destabilizing	0.879	D	0.431	neutral	None	None	None	None	I
V/N	0.1827	likely_benign	0.1689	benign	-0.441	Destabilizing	0.879	D	0.402	neutral	None	None	None	None	I
V/P	0.762	likely_pathogenic	0.757	pathogenic	-0.324	Destabilizing	0.937	D	0.385	neutral	None	None	None	None	I
V/Q	0.2155	likely_benign	0.2077	benign	-0.615	Destabilizing	0.785	D	0.372	neutral	None	None	None	None	I
V/R	0.1891	likely_benign	0.1841	benign	-0.076	Destabilizing	0.879	D	0.401	neutral	None	None	None	None	I
V/S	0.1446	likely_benign	0.139	benign	-0.831	Destabilizing	0.675	D	0.315	neutral	None	None	None	None	I
V/T	0.1325	likely_benign	0.1239	benign	-0.793	Destabilizing	0.675	D	0.269	neutral	None	None	None	None	I
V/W	0.7965	likely_pathogenic	0.7895	pathogenic	-0.689	Destabilizing	0.994	D	0.442	neutral	None	None	None	None	I
V/Y	0.4832	ambiguous	0.4661	ambiguous	-0.399	Destabilizing	0.978	D	0.419	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.