TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21550	64873;64874;64875	chr2:178585096;178585095;178585094	chr2:179449823;179449822;179449821
N2AB	19909	59950;59951;59952	chr2:178585096;178585095;178585094	chr2:179449823;179449822;179449821
N2A	18982	57169;57170;57171	chr2:178585096;178585095;178585094	chr2:179449823;179449822;179449821
N2B	12485	37678;37679;37680	chr2:178585096;178585095;178585094	chr2:179449823;179449822;179449821
Novex-1	12610	38053;38054;38055	chr2:178585096;178585095;178585094	chr2:179449823;179449822;179449821
Novex-2	12677	38254;38255;38256	chr2:178585096;178585095;178585094	chr2:179449823;179449822;179449821
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-124
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.2214
• 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
Q/H	None	None	0.999	N	0.591	0.301	0.40218521252	gnomAD-4.0.0	1.61222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89086E-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
Q/A	0.2786	likely_benign	0.313	benign	-0.721	Destabilizing	0.931	D	0.601	neutral	None	None	None	None	N
Q/C	0.5957	likely_pathogenic	0.6362	pathogenic	-0.215	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Q/D	0.6777	likely_pathogenic	0.6978	pathogenic	-1.248	Destabilizing	0.985	D	0.543	neutral	None	None	None	None	N
Q/E	0.1247	likely_benign	0.134	benign	-1.095	Destabilizing	0.953	D	0.527	neutral	N	0.483764087	None	None	N
Q/F	0.8239	likely_pathogenic	0.8421	pathogenic	-0.323	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
Q/G	0.3569	ambiguous	0.3813	ambiguous	-1.127	Destabilizing	0.985	D	0.707	prob.neutral	None	None	None	None	N
Q/H	0.3244	likely_benign	0.3374	benign	-1.037	Destabilizing	0.999	D	0.591	neutral	N	0.474203242	None	None	N
Q/I	0.5601	ambiguous	0.6178	pathogenic	0.344	Stabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
Q/K	0.117	likely_benign	0.1276	benign	-0.508	Destabilizing	0.98	D	0.567	neutral	N	0.441800035	None	None	N
Q/L	0.2705	likely_benign	0.3153	benign	0.344	Stabilizing	0.99	D	0.733	prob.delet.	N	0.482476008	None	None	N
Q/M	0.4923	ambiguous	0.5319	ambiguous	0.762	Stabilizing	0.999	D	0.597	neutral	None	None	None	None	N
Q/N	0.5269	ambiguous	0.5281	ambiguous	-1.195	Destabilizing	0.985	D	0.575	neutral	None	None	None	None	N
Q/P	0.859	likely_pathogenic	0.9148	pathogenic	0.02	Stabilizing	0.997	D	0.699	prob.neutral	D	0.533366188	None	None	N
Q/R	0.1182	likely_benign	0.1316	benign	-0.545	Destabilizing	0.99	D	0.593	neutral	N	0.487055109	None	None	N
Q/S	0.3704	ambiguous	0.3788	ambiguous	-1.28	Destabilizing	0.719	D	0.344	neutral	None	None	None	None	N
Q/T	0.3367	likely_benign	0.3613	ambiguous	-0.929	Destabilizing	0.971	D	0.618	neutral	None	None	None	None	N
Q/V	0.342	ambiguous	0.4114	ambiguous	0.02	Stabilizing	0.998	D	0.75	deleterious	None	None	None	None	N
Q/W	0.7133	likely_pathogenic	0.7678	pathogenic	-0.268	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Q/Y	0.6027	likely_pathogenic	0.6242	pathogenic	0.017	Stabilizing	0.999	D	0.728	prob.delet.	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.