TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21033	63322;63323;63324	chr2:178588628;178588627;178588626	chr2:179453355;179453354;179453353
N2AB	19392	58399;58400;58401	chr2:178588628;178588627;178588626	chr2:179453355;179453354;179453353
N2A	18465	55618;55619;55620	chr2:178588628;178588627;178588626	chr2:179453355;179453354;179453353
N2B	11968	36127;36128;36129	chr2:178588628;178588627;178588626	chr2:179453355;179453354;179453353
Novex-1	12093	36502;36503;36504	chr2:178588628;178588627;178588626	chr2:179453355;179453354;179453353
Novex-2	12160	36703;36704;36705	chr2:178588628;178588627;178588626	chr2:179453355;179453354;179453353
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-40
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2511
• 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
E/K	None	None	0.992	N	0.523	0.372	0.366466682447	gnomAD-4.0.0	6.9166E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04753E-07	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
E/A	0.198	likely_benign	0.1898	benign	-0.908	Destabilizing	0.996	D	0.583	neutral	N	0.473232117	None	None	N
E/C	0.8319	likely_pathogenic	0.8117	pathogenic	-0.746	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/D	0.2292	likely_benign	0.2199	benign	-1.555	Destabilizing	0.275	N	0.203	neutral	N	0.477712402	None	None	N
E/F	0.7954	likely_pathogenic	0.7778	pathogenic	-0.278	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/G	0.356	ambiguous	0.37	ambiguous	-1.341	Destabilizing	0.998	D	0.668	neutral	N	0.478436357	None	None	N
E/H	0.5989	likely_pathogenic	0.5598	ambiguous	-0.795	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/I	0.3619	ambiguous	0.3106	benign	0.305	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/K	0.3093	likely_benign	0.2962	benign	-1.594	Destabilizing	0.992	D	0.523	neutral	N	0.512766338	None	None	N
E/L	0.4619	ambiguous	0.4253	ambiguous	0.305	Stabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
E/M	0.4843	ambiguous	0.4483	ambiguous	0.915	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/N	0.4077	ambiguous	0.3963	ambiguous	-1.919	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
E/P	0.6202	likely_pathogenic	0.598	pathogenic	-0.08	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/Q	0.1786	likely_benign	0.1677	benign	-1.632	Destabilizing	0.999	D	0.644	neutral	N	0.521540537	None	None	N
E/R	0.4529	ambiguous	0.4238	ambiguous	-1.364	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/S	0.2638	likely_benign	0.2439	benign	-2.386	Highly Destabilizing	0.994	D	0.564	neutral	None	None	None	None	N
E/T	0.2581	likely_benign	0.2193	benign	-2.026	Highly Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
E/V	0.2289	likely_benign	0.2045	benign	-0.08	Destabilizing	1.0	D	0.769	deleterious	N	0.470131471	None	None	N
E/W	0.9254	likely_pathogenic	0.9174	pathogenic	-0.265	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/Y	0.6982	likely_pathogenic	0.6814	pathogenic	-0.146	Destabilizing	1.0	D	0.777	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.