TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13785	41578;41579;41580	chr2:178636218;178636217;178636216	chr2:179500945;179500944;179500943
N2AB	12144	36655;36656;36657	chr2:178636218;178636217;178636216	chr2:179500945;179500944;179500943
N2A	11217	33874;33875;33876	chr2:178636218;178636217;178636216	chr2:179500945;179500944;179500943
N2B	4720	14383;14384;14385	chr2:178636218;178636217;178636216	chr2:179500945;179500944;179500943
Novex-1	4845	14758;14759;14760	chr2:178636218;178636217;178636216	chr2:179500945;179500944;179500943
Novex-2	4912	14959;14960;14961	chr2:178636218;178636217;178636216	chr2:179500945;179500944;179500943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-88
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.2186
• 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
T/A	None	None	0.953	N	0.506	0.185	0.264547087235	gnomAD-4.0.0	2.09016E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.73468E-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
T/A	0.1355	likely_benign	0.162	benign	-0.799	Destabilizing	0.953	D	0.506	neutral	N	0.497969762	None	None	N
T/C	0.6394	likely_pathogenic	0.6884	pathogenic	-0.407	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
T/D	0.5933	likely_pathogenic	0.6705	pathogenic	0.317	Stabilizing	0.971	D	0.641	neutral	None	None	None	None	N
T/E	0.3897	ambiguous	0.4707	ambiguous	0.313	Stabilizing	0.271	N	0.319	neutral	None	None	None	None	N
T/F	0.4856	ambiguous	0.5562	ambiguous	-0.89	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
T/G	0.4108	ambiguous	0.435	ambiguous	-1.045	Destabilizing	0.993	D	0.728	deleterious	None	None	None	None	N
T/H	0.4101	ambiguous	0.4942	ambiguous	-1.258	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/I	0.3365	likely_benign	0.398	ambiguous	-0.239	Destabilizing	0.999	D	0.682	prob.neutral	N	0.492155349	None	None	N
T/K	0.2691	likely_benign	0.3138	benign	-0.514	Destabilizing	0.98	D	0.657	prob.neutral	N	0.447812794	None	None	N
T/L	0.1769	likely_benign	0.2036	benign	-0.239	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	N
T/M	0.1118	likely_benign	0.1326	benign	-0.051	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
T/N	0.1854	likely_benign	0.2092	benign	-0.37	Destabilizing	0.993	D	0.569	neutral	None	None	None	None	N
T/P	0.1139	likely_benign	0.142	benign	-0.394	Destabilizing	0.999	D	0.682	prob.neutral	N	0.471144524	None	None	N
T/Q	0.3016	likely_benign	0.3505	ambiguous	-0.504	Destabilizing	0.996	D	0.694	prob.delet.	None	None	None	None	N
T/R	0.2498	likely_benign	0.3083	benign	-0.345	Destabilizing	0.994	D	0.679	prob.neutral	N	0.491831085	None	None	N
T/S	0.2109	likely_benign	0.2411	benign	-0.729	Destabilizing	0.953	D	0.548	neutral	N	0.489905861	None	None	N
T/V	0.2493	likely_benign	0.2754	benign	-0.394	Destabilizing	0.993	D	0.532	neutral	None	None	None	None	N
T/W	0.8325	likely_pathogenic	0.8798	pathogenic	-0.801	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/Y	0.4769	ambiguous	0.5641	pathogenic	-0.569	Destabilizing	0.999	D	0.763	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.