TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29490	88693;88694;88695	chr2:178554991;178554990;178554989	chr2:179419718;179419717;179419716
N2AB	27849	83770;83771;83772	chr2:178554991;178554990;178554989	chr2:179419718;179419717;179419716
N2A	26922	80989;80990;80991	chr2:178554991;178554990;178554989	chr2:179419718;179419717;179419716
N2B	20425	61498;61499;61500	chr2:178554991;178554990;178554989	chr2:179419718;179419717;179419716
Novex-1	20550	61873;61874;61875	chr2:178554991;178554990;178554989	chr2:179419718;179419717;179419716
Novex-2	20617	62074;62075;62076	chr2:178554991;178554990;178554989	chr2:179419718;179419717;179419716
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: Ig-146
• Domain position: 47
• Structural Position: 125
• Q(SASA): 0.6699
• 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	rs1387328093	-0.291	0.684	N	0.405	0.362	0.440394187108	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/G	rs1387328093	-0.291	0.684	N	0.405	0.362	0.440394187108	gnomAD-4.0.0	4.77458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29836E-05	0
E/K	rs1466195239	0.905	0.012	N	0.13	0.263	0.280987212366	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1466195239	0.905	0.012	N	0.13	0.263	0.280987212366	gnomAD-4.0.0	4.77493E-06	None	None	None	None	N	None	0	0	None	4.7669E-05	0	None	0	0	0	2.86582E-05	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	0.3049	likely_benign	0.2691	benign	-0.616	Destabilizing	0.309	N	0.356	neutral	N	0.482249743	None	None	N
E/C	0.9084	likely_pathogenic	0.8972	pathogenic	-0.108	Destabilizing	0.996	D	0.431	neutral	None	None	None	None	N
E/D	0.2198	likely_benign	0.1963	benign	-0.542	Destabilizing	0.007	N	0.159	neutral	N	0.517570017	None	None	N
E/F	0.8835	likely_pathogenic	0.8519	pathogenic	-0.438	Destabilizing	0.984	D	0.425	neutral	None	None	None	None	N
E/G	0.3361	likely_benign	0.2879	benign	-0.866	Destabilizing	0.684	D	0.405	neutral	N	0.502128425	None	None	N
E/H	0.5846	likely_pathogenic	0.5393	ambiguous	-0.501	Destabilizing	0.984	D	0.382	neutral	None	None	None	None	N
E/I	0.5339	ambiguous	0.489	ambiguous	0.029	Stabilizing	0.953	D	0.434	neutral	None	None	None	None	N
E/K	0.2334	likely_benign	0.1972	benign	0.011	Stabilizing	0.012	N	0.13	neutral	N	0.480262422	None	None	N
E/L	0.593	likely_pathogenic	0.5436	ambiguous	0.029	Stabilizing	0.854	D	0.412	neutral	None	None	None	None	N
E/M	0.6239	likely_pathogenic	0.5815	pathogenic	0.346	Stabilizing	0.996	D	0.408	neutral	None	None	None	None	N
E/N	0.4264	ambiguous	0.387	ambiguous	-0.318	Destabilizing	0.59	D	0.315	neutral	None	None	None	None	N
E/P	0.9597	likely_pathogenic	0.9401	pathogenic	-0.165	Destabilizing	0.953	D	0.374	neutral	None	None	None	None	N
E/Q	0.1738	likely_benign	0.1565	benign	-0.263	Destabilizing	0.684	D	0.383	neutral	D	0.532288753	None	None	N
E/R	0.374	ambiguous	0.3254	benign	0.176	Stabilizing	0.59	D	0.359	neutral	None	None	None	None	N
E/S	0.3312	likely_benign	0.3027	benign	-0.525	Destabilizing	0.101	N	0.166	neutral	None	None	None	None	N
E/T	0.33	likely_benign	0.2993	benign	-0.322	Destabilizing	0.59	D	0.361	neutral	None	None	None	None	N
E/V	0.3391	likely_benign	0.3029	benign	-0.165	Destabilizing	0.815	D	0.408	neutral	D	0.528864446	None	None	N
E/W	0.9436	likely_pathogenic	0.9243	pathogenic	-0.256	Destabilizing	0.996	D	0.522	neutral	None	None	None	None	N
E/Y	0.7858	likely_pathogenic	0.7351	pathogenic	-0.198	Destabilizing	0.984	D	0.428	neutral	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.