TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30914	92965;92966;92967	chr2:178548886;178548885;178548884	chr2:179413613;179413612;179413611
N2AB	29273	88042;88043;88044	chr2:178548886;178548885;178548884	chr2:179413613;179413612;179413611
N2A	28346	85261;85262;85263	chr2:178548886;178548885;178548884	chr2:179413613;179413612;179413611
N2B	21849	65770;65771;65772	chr2:178548886;178548885;178548884	chr2:179413613;179413612;179413611
Novex-1	21974	66145;66146;66147	chr2:178548886;178548885;178548884	chr2:179413613;179413612;179413611
Novex-2	22041	66346;66347;66348	chr2:178548886;178548885;178548884	chr2:179413613;179413612;179413611
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-113
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.289
• 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	rs951807675	-2.554	0.791	N	0.583	0.33	0.801104325881	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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	0.3687	ambiguous	0.3728	ambiguous	-2.082	Highly Destabilizing	0.338	N	0.423	neutral	None	None	None	None	N
I/C	0.6786	likely_pathogenic	0.6864	pathogenic	-1.483	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
I/D	0.8743	likely_pathogenic	0.8725	pathogenic	-1.745	Destabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	N
I/E	0.6915	likely_pathogenic	0.6971	pathogenic	-1.563	Destabilizing	0.946	D	0.697	prob.delet.	None	None	None	None	N
I/F	0.2	likely_benign	0.2083	benign	-1.144	Destabilizing	0.868	D	0.494	neutral	N	0.508350314	None	None	N
I/G	0.752	likely_pathogenic	0.7648	pathogenic	-2.57	Highly Destabilizing	0.834	D	0.687	prob.delet.	None	None	None	None	N
I/H	0.6343	likely_pathogenic	0.6415	pathogenic	-1.669	Destabilizing	0.995	D	0.705	prob.delet.	None	None	None	None	N
I/K	0.5618	ambiguous	0.5841	pathogenic	-1.546	Destabilizing	0.946	D	0.697	prob.delet.	None	None	None	None	N
I/L	0.1473	likely_benign	0.1554	benign	-0.712	Destabilizing	0.068	N	0.387	neutral	N	0.477854048	None	None	N
I/M	0.12	likely_benign	0.1283	benign	-0.726	Destabilizing	0.93	D	0.505	neutral	N	0.501058982	None	None	N
I/N	0.5102	ambiguous	0.508	ambiguous	-1.796	Destabilizing	0.976	D	0.701	prob.delet.	N	0.481916894	None	None	N
I/P	0.873	likely_pathogenic	0.8792	pathogenic	-1.145	Destabilizing	0.982	D	0.709	prob.delet.	None	None	None	None	N
I/Q	0.5485	ambiguous	0.5544	ambiguous	-1.702	Destabilizing	0.982	D	0.706	prob.delet.	None	None	None	None	N
I/R	0.4856	ambiguous	0.5093	ambiguous	-1.216	Destabilizing	0.946	D	0.696	prob.delet.	None	None	None	None	N
I/S	0.4399	ambiguous	0.4412	ambiguous	-2.534	Highly Destabilizing	0.791	D	0.583	neutral	N	0.481156425	None	None	N
I/T	0.2909	likely_benign	0.2911	benign	-2.195	Highly Destabilizing	0.651	D	0.583	neutral	N	0.49365022	None	None	N
I/V	0.0578	likely_benign	0.0582	benign	-1.145	Destabilizing	0.001	N	0.158	neutral	N	0.392827078	None	None	N
I/W	0.8271	likely_pathogenic	0.845	pathogenic	-1.333	Destabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
I/Y	0.6092	likely_pathogenic	0.6201	pathogenic	-1.063	Destabilizing	0.946	D	0.571	neutral	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.