TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28232	84919;84920;84921	chr2:178561438;178561437;178561436	chr2:179426165;179426164;179426163
N2AB	26591	79996;79997;79998	chr2:178561438;178561437;178561436	chr2:179426165;179426164;179426163
N2A	25664	77215;77216;77217	chr2:178561438;178561437;178561436	chr2:179426165;179426164;179426163
N2B	19167	57724;57725;57726	chr2:178561438;178561437;178561436	chr2:179426165;179426164;179426163
Novex-1	19292	58099;58100;58101	chr2:178561438;178561437;178561436	chr2:179426165;179426164;179426163
Novex-2	19359	58300;58301;58302	chr2:178561438;178561437;178561436	chr2:179426165;179426164;179426163
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: Fn3-93
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2032
• Predicted PPI site: I

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/D	rs397517730	-1.599	0.822	N	0.481	0.279	0.231873229951	gnomAD-2.1.1	2.49471E-04	None	None	None	None	I	None	0	0	None	0	0	None	1.99333E-03	None	0	0	1.65837E-04
E/D	rs397517730	-1.599	0.822	N	0.481	0.279	0.231873229951	gnomAD-3.1.2	5.92E-05	None	None	None	None	I	None	4.82E-05	0	0	0	0	None	0	0	0	1.44748E-03	0
E/D	rs397517730	-1.599	0.822	N	0.481	0.279	0.231873229951	1000 genomes	7.98722E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	4.1E-03	None
E/D	rs397517730	-1.599	0.822	N	0.481	0.279	0.231873229951	gnomAD-4.0.0	1.14634E-04	None	None	None	None	I	None	3.99765E-05	0	None	0	0	None	0	3.30033E-04	8.47619E-07	1.86633E-03	1.44037E-04

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	0.6724	likely_pathogenic	0.6431	pathogenic	-0.855	Destabilizing	0.698	D	0.543	neutral	N	0.464403344	None	None	I
E/C	0.9729	likely_pathogenic	0.9688	pathogenic	-0.53	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	I
E/D	0.9301	likely_pathogenic	0.9136	pathogenic	-1.583	Destabilizing	0.822	D	0.481	neutral	N	0.49984184	None	None	I
E/F	0.9898	likely_pathogenic	0.9882	pathogenic	-0.313	Destabilizing	0.956	D	0.787	deleterious	None	None	None	None	I
E/G	0.8596	likely_pathogenic	0.8365	pathogenic	-1.307	Destabilizing	0.971	D	0.688	prob.neutral	N	0.50658979	None	None	I
E/H	0.9476	likely_pathogenic	0.9397	pathogenic	-0.621	Destabilizing	0.994	D	0.593	neutral	None	None	None	None	I
E/I	0.8229	likely_pathogenic	0.8179	pathogenic	0.414	Stabilizing	0.787	D	0.716	prob.delet.	None	None	None	None	I
E/K	0.589	likely_pathogenic	0.5694	pathogenic	-1.088	Destabilizing	0.698	D	0.484	neutral	N	0.468544401	None	None	I
E/L	0.9117	likely_pathogenic	0.9103	pathogenic	0.414	Stabilizing	0.754	D	0.659	neutral	None	None	None	None	I
E/M	0.8507	likely_pathogenic	0.8294	pathogenic	1.052	Stabilizing	0.988	D	0.735	prob.delet.	None	None	None	None	I
E/N	0.9379	likely_pathogenic	0.9187	pathogenic	-1.588	Destabilizing	0.978	D	0.567	neutral	None	None	None	None	I
E/P	0.9995	likely_pathogenic	0.9994	pathogenic	0.012	Stabilizing	0.993	D	0.721	prob.delet.	None	None	None	None	I
E/Q	0.2895	likely_benign	0.2751	benign	-1.298	Destabilizing	0.294	N	0.353	neutral	N	0.509936676	None	None	I
E/R	0.7654	likely_pathogenic	0.7645	pathogenic	-0.916	Destabilizing	0.956	D	0.559	neutral	None	None	None	None	I
E/S	0.8072	likely_pathogenic	0.7606	pathogenic	-2.079	Highly Destabilizing	0.86	D	0.497	neutral	None	None	None	None	I
E/T	0.8234	likely_pathogenic	0.7946	pathogenic	-1.677	Destabilizing	0.86	D	0.634	neutral	None	None	None	None	I
E/V	0.5963	likely_pathogenic	0.5992	pathogenic	0.012	Stabilizing	0.032	N	0.416	neutral	N	0.468505767	None	None	I
E/W	0.9971	likely_pathogenic	0.9967	pathogenic	-0.275	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	I
E/Y	0.9844	likely_pathogenic	0.9813	pathogenic	-0.098	Destabilizing	0.978	D	0.754	deleterious	None	None	None	None	I

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.