TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29397	88414;88415;88416	chr2:178556965;178556964;178556963	chr2:179421692;179421691;179421690
N2AB	27756	83491;83492;83493	chr2:178556965;178556964;178556963	chr2:179421692;179421691;179421690
N2A	26829	80710;80711;80712	chr2:178556965;178556964;178556963	chr2:179421692;179421691;179421690
N2B	20332	61219;61220;61221	chr2:178556965;178556964;178556963	chr2:179421692;179421691;179421690
Novex-1	20457	61594;61595;61596	chr2:178556965;178556964;178556963	chr2:179421692;179421691;179421690
Novex-2	20524	61795;61796;61797	chr2:178556965;178556964;178556963	chr2:179421692;179421691;179421690
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: Fn3-102
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1164
• 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/T	rs1475393277	None	0.012	N	0.644	0.411	0.664245949781	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1475393277	None	0.012	N	0.644	0.411	0.664245949781	gnomAD-4.0.0	6.57194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47007E-05	0	0
I/V	rs1701748367	None	None	N	0.167	0.127	0.337135696972	gnomAD-4.0.0	1.36853E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99526E-07	1.15937E-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
I/A	0.4358	ambiguous	0.3224	benign	-1.917	Destabilizing	0.007	N	0.582	neutral	None	None	None	None	N
I/C	0.6755	likely_pathogenic	0.6167	pathogenic	-1.343	Destabilizing	0.356	N	0.763	deleterious	None	None	None	None	N
I/D	0.9716	likely_pathogenic	0.9435	pathogenic	-1.586	Destabilizing	0.356	N	0.777	deleterious	None	None	None	None	N
I/E	0.9553	likely_pathogenic	0.9201	pathogenic	-1.307	Destabilizing	0.136	N	0.749	deleterious	None	None	None	None	N
I/F	0.488	ambiguous	0.3471	ambiguous	-1.049	Destabilizing	0.055	N	0.662	neutral	D	0.522079254	None	None	N
I/G	0.8877	likely_pathogenic	0.7721	pathogenic	-2.485	Highly Destabilizing	0.136	N	0.745	deleterious	None	None	None	None	N
I/H	0.9264	likely_pathogenic	0.8816	pathogenic	-1.999	Destabilizing	0.864	D	0.815	deleterious	None	None	None	None	N
I/K	0.945	likely_pathogenic	0.9175	pathogenic	-1.233	Destabilizing	0.136	N	0.749	deleterious	None	None	None	None	N
I/L	0.1634	likely_benign	0.1356	benign	-0.265	Destabilizing	0.002	N	0.354	neutral	N	0.450962944	None	None	N
I/M	0.2241	likely_benign	0.1746	benign	-0.435	Destabilizing	0.171	N	0.663	neutral	N	0.483084393	None	None	N
I/N	0.7999	likely_pathogenic	0.6914	pathogenic	-1.693	Destabilizing	0.56	D	0.799	deleterious	N	0.501695627	None	None	N
I/P	0.9314	likely_pathogenic	0.8897	pathogenic	-0.798	Destabilizing	0.356	N	0.78	deleterious	None	None	None	None	N
I/Q	0.9156	likely_pathogenic	0.865	pathogenic	-1.367	Destabilizing	0.628	D	0.807	deleterious	None	None	None	None	N
I/R	0.9038	likely_pathogenic	0.8591	pathogenic	-1.373	Destabilizing	0.356	N	0.807	deleterious	None	None	None	None	N
I/S	0.6316	likely_pathogenic	0.496	ambiguous	-2.466	Highly Destabilizing	0.055	N	0.727	prob.delet.	N	0.486046907	None	None	N
I/T	0.4711	ambiguous	0.365	ambiguous	-2.008	Highly Destabilizing	0.012	N	0.644	neutral	N	0.478564942	None	None	N
I/V	0.0644	likely_benign	0.06	benign	-0.798	Destabilizing	None	N	0.167	neutral	N	0.349030654	None	None	N
I/W	0.9793	likely_pathogenic	0.9597	pathogenic	-1.312	Destabilizing	0.864	D	0.81	deleterious	None	None	None	None	N
I/Y	0.8806	likely_pathogenic	0.7984	pathogenic	-0.995	Destabilizing	0.356	N	0.773	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.