TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8694	26305;26306;26307	chr2:178715106;178715105;178715104	chr2:179579833;179579832;179579831
N2AB	8377	25354;25355;25356	chr2:178715106;178715105;178715104	chr2:179579833;179579832;179579831
N2A	7450	22573;22574;22575	chr2:178715106;178715105;178715104	chr2:179579833;179579832;179579831
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-72
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4615
• 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/Q	rs373247663	0.382	0.135	N	0.207	0.149	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	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	0.2727	likely_benign	0.2015	benign	0.005	Stabilizing	0.396	N	0.527	neutral	N	0.5148205	None	None	N
E/C	0.9395	likely_pathogenic	0.8865	pathogenic	0.045	Stabilizing	0.993	D	0.656	neutral	None	None	None	None	N
E/D	0.1482	likely_benign	0.1282	benign	-0.136	Destabilizing	0.001	N	0.174	neutral	N	0.462506168	None	None	N
E/F	0.8975	likely_pathogenic	0.8188	pathogenic	-0.075	Destabilizing	0.986	D	0.598	neutral	None	None	None	None	N
E/G	0.2246	likely_benign	0.1573	benign	-0.116	Destabilizing	0.813	D	0.497	neutral	N	0.507875885	None	None	N
E/H	0.5689	likely_pathogenic	0.4583	ambiguous	0.373	Stabilizing	0.942	D	0.52	neutral	None	None	None	None	N
E/I	0.6182	likely_pathogenic	0.4907	ambiguous	0.264	Stabilizing	0.915	D	0.6	neutral	None	None	None	None	N
E/K	0.1528	likely_benign	0.1205	benign	0.535	Stabilizing	0.008	N	0.242	neutral	N	0.457233634	None	None	N
E/L	0.658	likely_pathogenic	0.5367	ambiguous	0.264	Stabilizing	0.841	D	0.531	neutral	None	None	None	None	N
E/M	0.6726	likely_pathogenic	0.5654	pathogenic	0.156	Stabilizing	0.957	D	0.598	neutral	None	None	None	None	N
E/N	0.3254	likely_benign	0.2566	benign	0.377	Stabilizing	0.259	N	0.473	neutral	None	None	None	None	N
E/P	0.8867	likely_pathogenic	0.7599	pathogenic	0.196	Stabilizing	0.614	D	0.55	neutral	None	None	None	None	N
E/Q	0.1614	likely_benign	0.1329	benign	0.389	Stabilizing	0.135	N	0.207	neutral	N	0.509163964	None	None	N
E/R	0.2934	likely_benign	0.219	benign	0.67	Stabilizing	0.617	D	0.473	neutral	None	None	None	None	N
E/S	0.2795	likely_benign	0.2171	benign	0.218	Stabilizing	0.634	D	0.497	neutral	None	None	None	None	N
E/T	0.3474	ambiguous	0.2653	benign	0.322	Stabilizing	0.894	D	0.501	neutral	None	None	None	None	N
E/V	0.3954	ambiguous	0.3007	benign	0.196	Stabilizing	0.739	D	0.518	neutral	N	0.48643048	None	None	N
E/W	0.9466	likely_pathogenic	0.8931	pathogenic	-0.042	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/Y	0.7905	likely_pathogenic	0.6701	pathogenic	0.148	Stabilizing	0.995	D	0.589	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.