TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25100	75523;75524;75525	chr2:178570834;178570833;178570832	chr2:179435561;179435560;179435559
N2AB	23459	70600;70601;70602	chr2:178570834;178570833;178570832	chr2:179435561;179435560;179435559
N2A	22532	67819;67820;67821	chr2:178570834;178570833;178570832	chr2:179435561;179435560;179435559
N2B	16035	48328;48329;48330	chr2:178570834;178570833;178570832	chr2:179435561;179435560;179435559
Novex-1	16160	48703;48704;48705	chr2:178570834;178570833;178570832	chr2:179435561;179435560;179435559
Novex-2	16227	48904;48905;48906	chr2:178570834;178570833;178570832	chr2:179435561;179435560;179435559
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-70
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.2734
• 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/V	rs1314990516	-0.919	0.003	N	0.136	0.128	0.151104730317	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs1314990516	-0.919	0.003	N	0.136	0.128	0.151104730317	gnomAD-4.0.0	2.05288E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69869E-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
I/A	0.9038	likely_pathogenic	0.868	pathogenic	-2.244	Highly Destabilizing	0.587	D	0.653	prob.neutral	None	None	None	None	N
I/C	0.9352	likely_pathogenic	0.9189	pathogenic	-1.514	Destabilizing	0.996	D	0.729	deleterious	None	None	None	None	N
I/D	0.9949	likely_pathogenic	0.993	pathogenic	-1.907	Destabilizing	0.984	D	0.84	deleterious	None	None	None	None	N
I/E	0.9755	likely_pathogenic	0.9676	pathogenic	-1.746	Destabilizing	0.953	D	0.823	deleterious	None	None	None	None	N
I/F	0.5367	ambiguous	0.4652	ambiguous	-1.325	Destabilizing	0.02	N	0.271	neutral	None	None	None	None	N
I/G	0.9875	likely_pathogenic	0.982	pathogenic	-2.737	Highly Destabilizing	0.953	D	0.792	deleterious	None	None	None	None	N
I/H	0.9656	likely_pathogenic	0.9551	pathogenic	-1.92	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
I/K	0.9297	likely_pathogenic	0.914	pathogenic	-1.665	Destabilizing	0.938	D	0.828	deleterious	N	0.497212861	None	None	N
I/L	0.2931	likely_benign	0.2507	benign	-0.866	Destabilizing	0.162	N	0.389	neutral	N	0.45673839	None	None	N
I/M	0.28	likely_benign	0.243	benign	-0.747	Destabilizing	0.938	D	0.622	neutral	N	0.481390012	None	None	N
I/N	0.9363	likely_pathogenic	0.9234	pathogenic	-1.811	Destabilizing	0.984	D	0.841	deleterious	None	None	None	None	N
I/P	0.9955	likely_pathogenic	0.9926	pathogenic	-1.3	Destabilizing	0.984	D	0.845	deleterious	None	None	None	None	N
I/Q	0.9463	likely_pathogenic	0.9347	pathogenic	-1.768	Destabilizing	0.984	D	0.819	deleterious	None	None	None	None	N
I/R	0.9105	likely_pathogenic	0.891	pathogenic	-1.256	Destabilizing	0.938	D	0.836	deleterious	N	0.496705882	None	None	N
I/S	0.931	likely_pathogenic	0.9152	pathogenic	-2.562	Highly Destabilizing	0.953	D	0.759	deleterious	None	None	None	None	N
I/T	0.8106	likely_pathogenic	0.7769	pathogenic	-2.252	Highly Destabilizing	0.682	D	0.729	deleterious	N	0.494424476	None	None	N
I/V	0.0842	likely_benign	0.0761	benign	-1.3	Destabilizing	0.003	N	0.136	neutral	N	0.429808519	None	None	N
I/W	0.9781	likely_pathogenic	0.9702	pathogenic	-1.549	Destabilizing	0.996	D	0.832	deleterious	None	None	None	None	N
I/Y	0.9065	likely_pathogenic	0.8899	pathogenic	-1.282	Destabilizing	0.833	D	0.738	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.