TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32808	98647;98648;98649	chr2:178539643;178539642;178539641	chr2:179404370;179404369;179404368
N2AB	31167	93724;93725;93726	chr2:178539643;178539642;178539641	chr2:179404370;179404369;179404368
N2A	30240	90943;90944;90945	chr2:178539643;178539642;178539641	chr2:179404370;179404369;179404368
N2B	23743	71452;71453;71454	chr2:178539643;178539642;178539641	chr2:179404370;179404369;179404368
Novex-1	23868	71827;71828;71829	chr2:178539643;178539642;178539641	chr2:179404370;179404369;179404368
Novex-2	23935	72028;72029;72030	chr2:178539643;178539642;178539641	chr2:179404370;179404369;179404368
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-127
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.3537
• 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
I/S	None	None	1.0	N	0.761	0.454	0.772125089601	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/T	rs1388284089	-1.588	1.0	N	0.678	0.477	0.681610798959	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	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
I/A	0.667	likely_pathogenic	0.6968	pathogenic	-2.289	Highly Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
I/C	0.8095	likely_pathogenic	0.8198	pathogenic	-1.982	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
I/D	0.9299	likely_pathogenic	0.9429	pathogenic	-2.932	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
I/E	0.8275	likely_pathogenic	0.8639	pathogenic	-2.848	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
I/F	0.3587	ambiguous	0.366	ambiguous	-1.593	Destabilizing	1.0	D	0.65	neutral	N	0.47329825	None	None	N
I/G	0.9018	likely_pathogenic	0.9091	pathogenic	-2.689	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
I/H	0.7884	likely_pathogenic	0.817	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
I/K	0.6077	likely_pathogenic	0.6584	pathogenic	-1.819	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
I/L	0.215	likely_benign	0.2118	benign	-1.192	Destabilizing	0.993	D	0.215	neutral	N	0.471151789	None	None	N
I/M	0.2106	likely_benign	0.2153	benign	-1.195	Destabilizing	1.0	D	0.646	neutral	N	0.480273236	None	None	N
I/N	0.6188	likely_pathogenic	0.6462	pathogenic	-1.942	Destabilizing	1.0	D	0.811	deleterious	N	0.487906558	None	None	N
I/P	0.8834	likely_pathogenic	0.8938	pathogenic	-1.534	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
I/Q	0.6986	likely_pathogenic	0.744	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
I/R	0.5277	ambiguous	0.5777	pathogenic	-1.271	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
I/S	0.6218	likely_pathogenic	0.6473	pathogenic	-2.503	Highly Destabilizing	1.0	D	0.761	deleterious	N	0.473018307	None	None	N
I/T	0.4337	ambiguous	0.4642	ambiguous	-2.3	Highly Destabilizing	1.0	D	0.678	prob.neutral	N	0.51271041	None	None	N
I/V	0.1055	likely_benign	0.1058	benign	-1.534	Destabilizing	0.993	D	0.235	neutral	N	0.409292466	None	None	N
I/W	0.9158	likely_pathogenic	0.9297	pathogenic	-1.845	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
I/Y	0.74	likely_pathogenic	0.7611	pathogenic	-1.598	Destabilizing	1.0	D	0.757	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.