TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18647	56164;56165;56166	chr2:178600965;178600964;178600963	chr2:179465692;179465691;179465690
N2AB	17006	51241;51242;51243	chr2:178600965;178600964;178600963	chr2:179465692;179465691;179465690
N2A	16079	48460;48461;48462	chr2:178600965;178600964;178600963	chr2:179465692;179465691;179465690
N2B	9582	28969;28970;28971	chr2:178600965;178600964;178600963	chr2:179465692;179465691;179465690
Novex-1	9707	29344;29345;29346	chr2:178600965;178600964;178600963	chr2:179465692;179465691;179465690
Novex-2	9774	29545;29546;29547	chr2:178600965;178600964;178600963	chr2:179465692;179465691;179465690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-23
• Domain position: 69
• Structural Position: 94
• Q(SASA): 0.2845
• 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
E/G	rs2053260795	None	1.0	N	0.775	0.474	0.382592752248	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/G	rs2053260795	None	1.0	N	0.775	0.474	0.382592752248	gnomAD-4.0.0	2.47995E-06	None	None	None	None	N	None	0	1.66828E-05	None	0	0	None	0	0	2.54381E-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
E/A	0.2232	likely_benign	0.2092	benign	-0.598	Destabilizing	0.999	D	0.709	prob.delet.	N	0.492084421	None	None	N
E/C	0.8955	likely_pathogenic	0.8746	pathogenic	-0.168	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/D	0.231	likely_benign	0.2032	benign	-0.603	Destabilizing	0.999	D	0.446	neutral	N	0.461473513	None	None	N
E/F	0.8884	likely_pathogenic	0.8613	pathogenic	-0.277	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/G	0.218	likely_benign	0.2063	benign	-0.86	Destabilizing	1.0	D	0.775	deleterious	N	0.497548956	None	None	N
E/H	0.6166	likely_pathogenic	0.5957	pathogenic	-0.217	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/I	0.5841	likely_pathogenic	0.5411	ambiguous	0.082	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/K	0.1981	likely_benign	0.2077	benign	0.087	Stabilizing	0.999	D	0.557	neutral	N	0.461953515	None	None	N
E/L	0.5844	likely_pathogenic	0.5505	ambiguous	0.082	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/M	0.5927	likely_pathogenic	0.5724	pathogenic	0.301	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/N	0.378	ambiguous	0.3391	benign	-0.367	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.6222	likely_pathogenic	0.63	pathogenic	-0.123	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/Q	0.1849	likely_benign	0.1867	benign	-0.298	Destabilizing	1.0	D	0.601	neutral	N	0.482502146	None	None	N
E/R	0.3365	likely_benign	0.3496	ambiguous	0.335	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/S	0.2645	likely_benign	0.2449	benign	-0.549	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
E/T	0.2326	likely_benign	0.2102	benign	-0.331	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/V	0.352	ambiguous	0.3263	benign	-0.123	Destabilizing	1.0	D	0.822	deleterious	N	0.479424555	None	None	N
E/W	0.9501	likely_pathogenic	0.9357	pathogenic	-0.046	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/Y	0.8115	likely_pathogenic	0.7795	pathogenic	-0.016	Destabilizing	1.0	D	0.82	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.