TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19900	59923;59924;59925	chr2:178592206;178592205;178592204	chr2:179456933;179456932;179456931
N2AB	18259	55000;55001;55002	chr2:178592206;178592205;178592204	chr2:179456933;179456932;179456931
N2A	17332	52219;52220;52221	chr2:178592206;178592205;178592204	chr2:179456933;179456932;179456931
N2B	10835	32728;32729;32730	chr2:178592206;178592205;178592204	chr2:179456933;179456932;179456931
Novex-1	10960	33103;33104;33105	chr2:178592206;178592205;178592204	chr2:179456933;179456932;179456931
Novex-2	11027	33304;33305;33306	chr2:178592206;178592205;178592204	chr2:179456933;179456932;179456931
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: Fn3-32
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4545
• 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/D	rs1559600496	None	0.054	N	0.176	0.043	0.1749357433	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.04E-06	0
E/D	rs1559600496	None	0.054	N	0.176	0.043	0.1749357433	gnomAD-4.0.0	1.59508E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41779E-04	0	0	0
E/G	rs2050365298	None	0.978	N	0.593	0.416	0.361558571881	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs2050365298	None	0.978	N	0.593	0.416	0.361558571881	gnomAD-4.0.0	2.56759E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79375E-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	0.1688	likely_benign	0.1895	benign	-0.207	Destabilizing	0.989	D	0.547	neutral	N	0.402865139	None	None	N
E/C	0.8931	likely_pathogenic	0.9079	pathogenic	-0.392	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/D	0.108	likely_benign	0.1189	benign	-1.259	Destabilizing	0.054	N	0.176	neutral	N	0.451507235	None	None	N
E/F	0.8599	likely_pathogenic	0.8829	pathogenic	0.625	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
E/G	0.2692	likely_benign	0.3147	benign	-0.594	Destabilizing	0.978	D	0.593	neutral	N	0.462030873	None	None	N
E/H	0.7181	likely_pathogenic	0.7586	pathogenic	0.594	Stabilizing	0.999	D	0.539	neutral	None	None	None	None	N
E/I	0.4804	ambiguous	0.5393	ambiguous	0.847	Stabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
E/K	0.3597	ambiguous	0.4214	ambiguous	-0.322	Destabilizing	0.978	D	0.466	neutral	N	0.432516043	None	None	N
E/L	0.4846	ambiguous	0.5358	ambiguous	0.847	Stabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
E/M	0.5709	likely_pathogenic	0.5972	pathogenic	0.948	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/N	0.3461	ambiguous	0.4002	ambiguous	-1.035	Destabilizing	0.983	D	0.509	neutral	None	None	None	None	N
E/P	0.3275	likely_benign	0.3645	ambiguous	0.518	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/Q	0.2473	likely_benign	0.2698	benign	-0.825	Destabilizing	0.989	D	0.519	neutral	N	0.462030873	None	None	N
E/R	0.5525	ambiguous	0.6177	pathogenic	0.078	Stabilizing	0.998	D	0.543	neutral	None	None	None	None	N
E/S	0.2807	likely_benign	0.3275	benign	-1.281	Destabilizing	0.983	D	0.461	neutral	None	None	None	None	N
E/T	0.3434	ambiguous	0.3859	ambiguous	-0.937	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	N
E/V	0.2995	likely_benign	0.3344	benign	0.518	Stabilizing	0.999	D	0.675	neutral	N	0.480443276	None	None	N
E/W	0.959	likely_pathogenic	0.9703	pathogenic	0.83	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/Y	0.7351	likely_pathogenic	0.7762	pathogenic	0.887	Stabilizing	0.999	D	0.746	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.