TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17621	53086;53087;53088	chr2:178607926;178607925;178607924	chr2:179472653;179472652;179472651
N2AB	15980	48163;48164;48165	chr2:178607926;178607925;178607924	chr2:179472653;179472652;179472651
N2A	15053	45382;45383;45384	chr2:178607926;178607925;178607924	chr2:179472653;179472652;179472651
N2B	8556	25891;25892;25893	chr2:178607926;178607925;178607924	chr2:179472653;179472652;179472651
Novex-1	8681	26266;26267;26268	chr2:178607926;178607925;178607924	chr2:179472653;179472652;179472651
Novex-2	8748	26467;26468;26469	chr2:178607926;178607925;178607924	chr2:179472653;179472652;179472651
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: Fn3-16
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.8734
• 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	None	None	0.896	N	0.484	0.299	0.313518423057	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/Q	None	None	0.984	N	0.451	0.328	0.254244900254	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-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	0.2127	likely_benign	0.1747	benign	-0.028	Destabilizing	0.026	N	0.297	neutral	N	0.512648908	None	None	N
E/C	0.9155	likely_pathogenic	0.8516	pathogenic	-0.263	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
E/D	0.1179	likely_benign	0.1025	benign	-0.352	Destabilizing	0.011	N	0.173	neutral	N	0.479115124	None	None	N
E/F	0.8973	likely_pathogenic	0.8331	pathogenic	-0.039	Destabilizing	0.988	D	0.551	neutral	None	None	None	None	N
E/G	0.1543	likely_benign	0.1241	benign	-0.143	Destabilizing	0.811	D	0.439	neutral	N	0.468824344	None	None	N
E/H	0.5806	likely_pathogenic	0.4793	ambiguous	0.602	Stabilizing	0.999	D	0.428	neutral	None	None	None	None	N
E/I	0.6371	likely_pathogenic	0.5383	ambiguous	0.218	Stabilizing	0.976	D	0.55	neutral	None	None	None	None	N
E/K	0.2049	likely_benign	0.1588	benign	0.395	Stabilizing	0.896	D	0.484	neutral	N	0.47030364	None	None	N
E/L	0.6089	likely_pathogenic	0.5078	ambiguous	0.218	Stabilizing	0.976	D	0.489	neutral	None	None	None	None	N
E/M	0.6948	likely_pathogenic	0.5758	pathogenic	-0.044	Destabilizing	0.999	D	0.515	neutral	None	None	None	None	N
E/N	0.2961	likely_benign	0.2296	benign	0.099	Stabilizing	0.952	D	0.429	neutral	None	None	None	None	N
E/P	0.3806	ambiguous	0.3237	benign	0.154	Stabilizing	0.988	D	0.444	neutral	None	None	None	None	N
E/Q	0.1841	likely_benign	0.1507	benign	0.113	Stabilizing	0.984	D	0.451	neutral	N	0.512939696	None	None	N
E/R	0.3352	likely_benign	0.2628	benign	0.653	Stabilizing	0.988	D	0.443	neutral	None	None	None	None	N
E/S	0.2249	likely_benign	0.1818	benign	-0.026	Destabilizing	0.851	D	0.452	neutral	None	None	None	None	N
E/T	0.3006	likely_benign	0.2373	benign	0.079	Stabilizing	0.919	D	0.417	neutral	None	None	None	None	N
E/V	0.3875	ambiguous	0.3188	benign	0.154	Stabilizing	0.938	D	0.405	neutral	N	0.513318124	None	None	N
E/W	0.9245	likely_pathogenic	0.8684	pathogenic	0.015	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	N
E/Y	0.7776	likely_pathogenic	0.6835	pathogenic	0.185	Stabilizing	0.996	D	0.507	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.