TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6818	20677;20678;20679	chr2:178725870;178725869;178725868	chr2:179590597;179590596;179590595
N2AB	6501	19726;19727;19728	chr2:178725870;178725869;178725868	chr2:179590597;179590596;179590595
N2A	5574	16945;16946;16947	chr2:178725870;178725869;178725868	chr2:179590597;179590596;179590595
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-52
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.063
• 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	rs1371747838	-2.526	0.998	N	0.767	0.763	0.826127071158	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
I/T	rs1371747838	-2.526	0.998	N	0.767	0.763	0.826127071158	gnomAD-4.0.0	1.36887E-06	None	None	None	None	N	None	2.99079E-05	2.23874E-05	None	0	0	None	0	0	0	0	0
I/V	rs2079253032	None	0.003	N	0.227	0.167	0.619456947012	gnomAD-4.0.0	7.96229E-06	None	None	None	None	N	None	0	0	None	0	1.38727E-04	None	0	0	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	0.8239	likely_pathogenic	0.786	pathogenic	-2.511	Highly Destabilizing	0.938	D	0.733	prob.delet.	None	None	None	None	N
I/C	0.8987	likely_pathogenic	0.8878	pathogenic	-1.778	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
I/D	0.9981	likely_pathogenic	0.9981	pathogenic	-3.211	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/E	0.9953	likely_pathogenic	0.9949	pathogenic	-2.876	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/F	0.4499	ambiguous	0.4246	ambiguous	-1.514	Destabilizing	0.987	D	0.719	prob.delet.	N	0.505726588	None	None	N
I/G	0.9794	likely_pathogenic	0.9736	pathogenic	-3.125	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
I/H	0.9878	likely_pathogenic	0.9875	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/K	0.989	likely_pathogenic	0.9893	pathogenic	-1.816	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
I/L	0.1101	likely_benign	0.1026	benign	-0.652	Destabilizing	0.001	N	0.281	neutral	N	0.304575296	None	None	N
I/M	0.1887	likely_benign	0.1726	benign	-0.972	Destabilizing	0.959	D	0.643	neutral	N	0.515866224	None	None	N
I/N	0.9662	likely_pathogenic	0.9662	pathogenic	-2.589	Highly Destabilizing	1.0	D	0.878	deleterious	N	0.495569329	None	None	N
I/P	0.9936	likely_pathogenic	0.9926	pathogenic	-1.265	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/Q	0.9858	likely_pathogenic	0.9846	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
I/R	0.9809	likely_pathogenic	0.9819	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
I/S	0.9323	likely_pathogenic	0.9235	pathogenic	-3.082	Highly Destabilizing	1.0	D	0.837	deleterious	N	0.502317279	None	None	N
I/T	0.8922	likely_pathogenic	0.8671	pathogenic	-2.572	Highly Destabilizing	0.998	D	0.767	deleterious	N	0.502317279	None	None	N
I/V	0.1037	likely_benign	0.0919	benign	-1.265	Destabilizing	0.003	N	0.227	neutral	N	0.473942244	None	None	N
I/W	0.9823	likely_pathogenic	0.9813	pathogenic	-1.882	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/Y	0.9304	likely_pathogenic	0.9286	pathogenic	-1.699	Destabilizing	0.999	D	0.807	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.