TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29751	89476;89477;89478	chr2:178553754;178553753;178553752	chr2:179418481;179418480;179418479
N2AB	28110	84553;84554;84555	chr2:178553754;178553753;178553752	chr2:179418481;179418480;179418479
N2A	27183	81772;81773;81774	chr2:178553754;178553753;178553752	chr2:179418481;179418480;179418479
N2B	20686	62281;62282;62283	chr2:178553754;178553753;178553752	chr2:179418481;179418480;179418479
Novex-1	20811	62656;62657;62658	chr2:178553754;178553753;178553752	chr2:179418481;179418480;179418479
Novex-2	20878	62857;62858;62859	chr2:178553754;178553753;178553752	chr2:179418481;179418480;179418479
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: Fn3-105
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0818
• 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/F	rs1367538790	-1.648	0.991	N	0.744	0.37	0.462022758384	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
I/F	rs1367538790	-1.648	0.991	N	0.744	0.37	0.462022758384	gnomAD-4.0.0	1.59996E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87565E-06	0	0
I/T	rs397517742	None	0.939	N	0.769	0.51	0.688008359126	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/T	rs397517742	None	0.939	N	0.769	0.51	0.688008359126	gnomAD-4.0.0	2.57309E-06	None	None	None	None	N	None	0	3.40136E-05	None	0	0	None	0	0	0	0	0
I/V	rs1367538790	-1.235	0.02	N	0.209	0.079	None	gnomAD-2.1.1	7.22E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.58E-05	0
I/V	rs1367538790	-1.235	0.02	N	0.209	0.079	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/V	rs1367538790	-1.235	0.02	N	0.209	0.079	None	gnomAD-4.0.0	6.4333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.20259E-05	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	0.8132	likely_pathogenic	0.7988	pathogenic	-2.82	Highly Destabilizing	0.91	D	0.69	prob.neutral	None	None	None	None	N
I/C	0.908	likely_pathogenic	0.913	pathogenic	-2.711	Highly Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
I/D	0.9979	likely_pathogenic	0.9972	pathogenic	-3.006	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
I/E	0.9927	likely_pathogenic	0.9917	pathogenic	-2.71	Highly Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
I/F	0.6429	likely_pathogenic	0.6152	pathogenic	-1.821	Destabilizing	0.991	D	0.744	deleterious	N	0.481425325	None	None	N
I/G	0.9864	likely_pathogenic	0.9839	pathogenic	-3.414	Highly Destabilizing	0.993	D	0.844	deleterious	None	None	None	None	N
I/H	0.9896	likely_pathogenic	0.9867	pathogenic	-2.977	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
I/K	0.9848	likely_pathogenic	0.9819	pathogenic	-2.082	Highly Destabilizing	0.993	D	0.844	deleterious	None	None	None	None	N
I/L	0.257	likely_benign	0.2729	benign	-1.052	Destabilizing	0.58	D	0.351	neutral	N	0.489502689	None	None	N
I/M	0.2415	likely_benign	0.2585	benign	-1.488	Destabilizing	0.991	D	0.706	prob.neutral	N	0.520657889	None	None	N
I/N	0.9654	likely_pathogenic	0.9563	pathogenic	-2.641	Highly Destabilizing	0.997	D	0.846	deleterious	D	0.523256148	None	None	N
I/P	0.9984	likely_pathogenic	0.9975	pathogenic	-1.63	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9828	likely_pathogenic	0.9814	pathogenic	-2.359	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
I/R	0.9744	likely_pathogenic	0.9698	pathogenic	-2.052	Highly Destabilizing	0.993	D	0.851	deleterious	None	None	None	None	N
I/S	0.9352	likely_pathogenic	0.9193	pathogenic	-3.392	Highly Destabilizing	0.991	D	0.824	deleterious	N	0.493542099	None	None	N
I/T	0.9081	likely_pathogenic	0.8824	pathogenic	-2.922	Highly Destabilizing	0.939	D	0.769	deleterious	N	0.504809499	None	None	N
I/V	0.0826	likely_benign	0.0808	benign	-1.63	Destabilizing	0.02	N	0.209	neutral	N	0.455656687	None	None	N
I/W	0.9929	likely_pathogenic	0.9918	pathogenic	-2.064	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
I/Y	0.9589	likely_pathogenic	0.9517	pathogenic	-1.872	Destabilizing	0.998	D	0.799	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.