TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27042	81349;81350;81351	chr2:178565008;178565007;178565006	chr2:179429735;179429734;179429733
N2AB	25401	76426;76427;76428	chr2:178565008;178565007;178565006	chr2:179429735;179429734;179429733
N2A	24474	73645;73646;73647	chr2:178565008;178565007;178565006	chr2:179429735;179429734;179429733
N2B	17977	54154;54155;54156	chr2:178565008;178565007;178565006	chr2:179429735;179429734;179429733
Novex-1	18102	54529;54530;54531	chr2:178565008;178565007;178565006	chr2:179429735;179429734;179429733
Novex-2	18169	54730;54731;54732	chr2:178565008;178565007;178565006	chr2:179429735;179429734;179429733
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-84
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3237
• 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	rs766412271	-1.033	0.999	N	0.471	0.364	0.181679512989	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/D	rs766412271	-1.033	0.999	N	0.471	0.364	0.181679512989	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	None	0	0	0	0	0
E/V	None	None	1.0	N	0.799	0.592	0.612639375224	gnomAD-4.0.0	1.59263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86008E-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	0.2832	likely_benign	0.3236	benign	-1.068	Destabilizing	0.999	D	0.705	prob.neutral	N	0.485082174	None	None	N
E/C	0.935	likely_pathogenic	0.9466	pathogenic	-0.527	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/D	0.5477	ambiguous	0.577	pathogenic	-1.224	Destabilizing	0.999	D	0.471	neutral	N	0.472231385	None	None	N
E/F	0.9614	likely_pathogenic	0.9697	pathogenic	-0.596	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/G	0.4973	ambiguous	0.5323	ambiguous	-1.454	Destabilizing	1.0	D	0.767	deleterious	N	0.499173958	None	None	N
E/H	0.8334	likely_pathogenic	0.8617	pathogenic	-0.896	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
E/I	0.6971	likely_pathogenic	0.7353	pathogenic	None	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.444	ambiguous	0.4896	ambiguous	-0.726	Destabilizing	0.999	D	0.602	neutral	N	0.475812556	None	None	N
E/L	0.752	likely_pathogenic	0.7929	pathogenic	None	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/M	0.7397	likely_pathogenic	0.7813	pathogenic	0.574	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/N	0.6501	likely_pathogenic	0.6917	pathogenic	-1.177	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/P	0.8162	likely_pathogenic	0.8135	pathogenic	-0.336	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Q	0.2521	likely_benign	0.2758	benign	-1.032	Destabilizing	1.0	D	0.619	neutral	D	0.524234125	None	None	N
E/R	0.6197	likely_pathogenic	0.6689	pathogenic	-0.521	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/S	0.4461	ambiguous	0.5051	ambiguous	-1.583	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
E/T	0.4965	ambiguous	0.5489	ambiguous	-1.25	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/V	0.4715	ambiguous	0.5279	ambiguous	-0.336	Destabilizing	1.0	D	0.799	deleterious	N	0.481323193	None	None	N
E/W	0.9906	likely_pathogenic	0.9928	pathogenic	-0.362	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9278	likely_pathogenic	0.9417	pathogenic	-0.327	Destabilizing	1.0	D	0.778	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.