TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2512	7759;7760;7761	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247
N2AB	2512	7759;7760;7761	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247
N2A	2512	7759;7760;7761	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247
N2B	2466	7621;7622;7623	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247
Novex-1	2466	7621;7622;7623	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247
Novex-2	2466	7621;7622;7623	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247
Novex-3	2512	7759;7760;7761	chr2:178773522;178773521;178773520	chr2:179638249;179638248;179638247

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-14
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.4717
• 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/K	rs116049561	0.225	0.96	D	0.596	0.422	None	gnomAD-2.1.1	2.12E-05	None	None	None	None	N	None	4.01E-05	0	None	0	0	None	0	None	0	3.88E-05	0
E/K	rs116049561	0.225	0.96	D	0.596	0.422	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs116049561	0.225	0.96	D	0.596	0.422	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs116049561	0.225	0.96	D	0.596	0.422	None	gnomAD-4.0.0	4.39899E-05	None	None	None	None	N	None	2.66638E-05	0	None	0	0	None	0	0	5.59333E-05	0	4.8E-05

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	0.1354	likely_benign	0.1414	benign	-0.593	Destabilizing	0.026	N	0.318	neutral	N	0.481602594	None	None	N
E/C	0.8535	likely_pathogenic	0.8633	pathogenic	-0.052	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
E/D	0.2695	likely_benign	0.3035	benign	-0.544	Destabilizing	0.896	D	0.567	neutral	N	0.516844787	None	None	N
E/F	0.8586	likely_pathogenic	0.8626	pathogenic	-0.354	Destabilizing	0.988	D	0.697	prob.neutral	None	None	None	None	N
E/G	0.1947	likely_benign	0.2053	benign	-0.843	Destabilizing	0.026	N	0.34	neutral	N	0.51796114	None	None	N
E/H	0.6087	likely_pathogenic	0.6375	pathogenic	-0.314	Destabilizing	0.988	D	0.57	neutral	None	None	None	None	N
E/I	0.5694	likely_pathogenic	0.5774	pathogenic	0.05	Stabilizing	0.976	D	0.707	prob.neutral	None	None	None	None	N
E/K	0.1613	likely_benign	0.1676	benign	0.251	Stabilizing	0.96	D	0.596	neutral	D	0.602166284	None	None	N
E/L	0.6341	likely_pathogenic	0.6549	pathogenic	0.05	Stabilizing	0.976	D	0.65	neutral	None	None	None	None	N
E/M	0.5612	ambiguous	0.5697	pathogenic	0.304	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/N	0.3913	ambiguous	0.4224	ambiguous	-0.184	Destabilizing	0.988	D	0.587	neutral	None	None	None	None	N
E/P	0.9511	likely_pathogenic	0.9634	pathogenic	-0.144	Destabilizing	0.988	D	0.715	prob.delet.	None	None	None	None	N
E/Q	0.1507	likely_benign	0.1557	benign	-0.137	Destabilizing	0.663	D	0.221	neutral	N	0.514609972	None	None	N
E/R	0.27	likely_benign	0.2821	benign	0.43	Stabilizing	0.976	D	0.596	neutral	None	None	None	None	N
E/S	0.1993	likely_benign	0.2121	benign	-0.366	Destabilizing	0.851	D	0.589	neutral	None	None	None	None	N
E/T	0.2805	likely_benign	0.2926	benign	-0.156	Destabilizing	0.919	D	0.649	neutral	None	None	None	None	N
E/V	0.3573	ambiguous	0.3659	ambiguous	-0.144	Destabilizing	0.938	D	0.641	neutral	N	0.512401891	None	None	N
E/W	0.9616	likely_pathogenic	0.9653	pathogenic	-0.131	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/Y	0.7851	likely_pathogenic	0.8007	pathogenic	-0.081	Destabilizing	0.996	D	0.707	prob.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.