TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2946	9061;9062;9063	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470
N2AB	2946	9061;9062;9063	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470
N2A	2946	9061;9062;9063	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470
N2B	2900	8923;8924;8925	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470
Novex-1	2900	8923;8924;8925	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470
Novex-2	2900	8923;8924;8925	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470
Novex-3	2946	9061;9062;9063	chr2:178769745;178769744;178769743	chr2:179634472;179634471;179634470

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-19
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.3985
• 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	None	None	0.031	N	0.163	0.298	0.280987212366	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

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	0.1812	likely_benign	0.2035	benign	-0.054	Destabilizing	0.248	N	0.236	neutral	D	0.524941839	None	None	N
E/C	0.9479	likely_pathogenic	0.9579	pathogenic	0.196	Stabilizing	1.0	D	0.555	neutral	None	None	None	None	N
E/D	0.1318	likely_benign	0.1363	benign	-0.137	Destabilizing	0.031	N	0.163	neutral	N	0.4841355	None	None	N
E/F	0.9153	likely_pathogenic	0.9317	pathogenic	-0.192	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
E/G	0.2325	likely_benign	0.2481	benign	-0.156	Destabilizing	0.961	D	0.463	neutral	D	0.525369318	None	None	N
E/H	0.7257	likely_pathogenic	0.7581	pathogenic	0.17	Stabilizing	0.999	D	0.437	neutral	None	None	None	None	N
E/I	0.6295	likely_pathogenic	0.6658	pathogenic	0.155	Stabilizing	0.996	D	0.529	neutral	None	None	None	None	N
E/K	0.2325	likely_benign	0.2516	benign	0.642	Stabilizing	0.961	D	0.495	neutral	D	0.579033094	None	None	N
E/L	0.6442	likely_pathogenic	0.677	pathogenic	0.155	Stabilizing	0.97	D	0.453	neutral	None	None	None	None	N
E/M	0.645	likely_pathogenic	0.6861	pathogenic	0.189	Stabilizing	1.0	D	0.503	neutral	None	None	None	None	N
E/N	0.3639	ambiguous	0.3833	ambiguous	0.468	Stabilizing	0.97	D	0.439	neutral	None	None	None	None	N
E/P	0.9032	likely_pathogenic	0.9225	pathogenic	0.103	Stabilizing	0.996	D	0.432	neutral	None	None	None	None	N
E/Q	0.2455	likely_benign	0.267	benign	0.475	Stabilizing	0.98	D	0.452	neutral	D	0.634138585	None	None	N
E/R	0.4377	ambiguous	0.4763	ambiguous	0.666	Stabilizing	0.996	D	0.429	neutral	None	None	None	None	N
E/S	0.2566	likely_benign	0.2715	benign	0.341	Stabilizing	0.942	D	0.478	neutral	None	None	None	None	N
E/T	0.3185	likely_benign	0.3426	ambiguous	0.435	Stabilizing	0.97	D	0.457	neutral	None	None	None	None	N
E/V	0.3939	ambiguous	0.4339	ambiguous	0.103	Stabilizing	0.961	D	0.428	neutral	D	0.581967026	None	None	N
E/W	0.9685	likely_pathogenic	0.9758	pathogenic	-0.171	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/Y	0.8516	likely_pathogenic	0.8738	pathogenic	0.024	Stabilizing	0.999	D	0.506	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.