TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27999	84220;84221;84222	chr2:178562137;178562136;178562135	chr2:179426864;179426863;179426862
N2AB	26358	79297;79298;79299	chr2:178562137;178562136;178562135	chr2:179426864;179426863;179426862
N2A	25431	76516;76517;76518	chr2:178562137;178562136;178562135	chr2:179426864;179426863;179426862
N2B	18934	57025;57026;57027	chr2:178562137;178562136;178562135	chr2:179426864;179426863;179426862
Novex-1	19059	57400;57401;57402	chr2:178562137;178562136;178562135	chr2:179426864;179426863;179426862
Novex-2	19126	57601;57602;57603	chr2:178562137;178562136;178562135	chr2:179426864;179426863;179426862
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-142
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.9201
• 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
D/V	None	None	0.999	N	0.691	0.538	0.547039986869	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85994E-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
D/A	0.3313	likely_benign	0.2602	benign	-0.604	Destabilizing	0.999	D	0.645	neutral	N	0.497579526	None	None	N
D/C	0.7255	likely_pathogenic	0.6726	pathogenic	-0.148	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/E	0.3393	likely_benign	0.2828	benign	-0.437	Destabilizing	0.767	D	0.383	neutral	N	0.469307053	None	None	N
D/F	0.8139	likely_pathogenic	0.7653	pathogenic	-0.315	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
D/G	0.1831	likely_benign	0.1496	benign	-0.868	Destabilizing	0.998	D	0.688	prob.neutral	N	0.469912483	None	None	N
D/H	0.5774	likely_pathogenic	0.5301	ambiguous	-0.352	Destabilizing	1.0	D	0.646	neutral	N	0.520799115	None	None	N
D/I	0.8259	likely_pathogenic	0.7471	pathogenic	0.067	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
D/K	0.7292	likely_pathogenic	0.6796	pathogenic	0.023	Stabilizing	0.999	D	0.671	neutral	None	None	None	None	N
D/L	0.7127	likely_pathogenic	0.6326	pathogenic	0.067	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/M	0.8585	likely_pathogenic	0.8034	pathogenic	0.358	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
D/N	0.1144	likely_benign	0.1034	benign	-0.4	Destabilizing	0.999	D	0.64	neutral	N	0.454994098	None	None	N
D/P	0.9808	likely_pathogenic	0.9717	pathogenic	-0.134	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
D/Q	0.6137	likely_pathogenic	0.5432	ambiguous	-0.329	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
D/R	0.6961	likely_pathogenic	0.6588	pathogenic	0.215	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
D/S	0.2454	likely_benign	0.2047	benign	-0.55	Destabilizing	0.997	D	0.63	neutral	None	None	None	None	N
D/T	0.6637	likely_pathogenic	0.5842	pathogenic	-0.335	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/V	0.6275	likely_pathogenic	0.527	ambiguous	-0.134	Destabilizing	0.999	D	0.691	prob.neutral	N	0.498339994	None	None	N
D/W	0.9442	likely_pathogenic	0.931	pathogenic	-0.08	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
D/Y	0.3796	ambiguous	0.3343	benign	-0.057	Destabilizing	1.0	D	0.653	neutral	N	0.5096963	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.