TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1020	3283;3284;3285	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573
N2AB	1020	3283;3284;3285	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573
N2A	1020	3283;3284;3285	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573
N2B	974	3145;3146;3147	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573
Novex-1	974	3145;3146;3147	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573
Novex-2	974	3145;3146;3147	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573
Novex-3	1020	3283;3284;3285	chr2:178782848;178782847;178782846	chr2:179647575;179647574;179647573

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-3
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9383
• Predicted PPI site: I

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/A	None	None	0.896	N	0.438	0.463	0.487843537783	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.1773	likely_benign	0.1995	benign	0.017	Stabilizing	0.896	D	0.438	neutral	N	0.51573258	None	None	I
E/C	0.9554	likely_pathogenic	0.9674	pathogenic	-0.052	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	I
E/D	0.2165	likely_benign	0.2143	benign	-0.285	Destabilizing	0.896	D	0.423	neutral	N	0.515130282	None	None	I
E/F	0.9151	likely_pathogenic	0.9356	pathogenic	-0.082	Destabilizing	0.996	D	0.573	neutral	None	None	None	None	I
E/G	0.2364	likely_benign	0.2801	benign	-0.093	Destabilizing	0.896	D	0.415	neutral	N	0.517255003	None	None	I
E/H	0.5913	likely_pathogenic	0.6576	pathogenic	0.459	Stabilizing	0.988	D	0.426	neutral	None	None	None	None	I
E/I	0.5752	likely_pathogenic	0.6201	pathogenic	0.245	Stabilizing	0.988	D	0.571	neutral	None	None	None	None	I
E/K	0.1066	likely_benign	0.1368	benign	0.491	Stabilizing	0.026	N	0.43	neutral	N	0.502171735	None	None	I
E/L	0.584	likely_pathogenic	0.6503	pathogenic	0.245	Stabilizing	0.976	D	0.474	neutral	None	None	None	None	I
E/M	0.6165	likely_pathogenic	0.6726	pathogenic	0.079	Stabilizing	0.999	D	0.542	neutral	None	None	None	None	I
E/N	0.3898	ambiguous	0.4129	ambiguous	0.302	Stabilizing	0.976	D	0.402	neutral	None	None	None	None	I
E/P	0.6017	likely_pathogenic	0.6327	pathogenic	0.187	Stabilizing	0.988	D	0.444	neutral	None	None	None	None	I
E/Q	0.162	likely_benign	0.1851	benign	0.303	Stabilizing	0.103	N	0.339	neutral	N	0.507214285	None	None	I
E/R	0.2298	likely_benign	0.2981	benign	0.663	Stabilizing	0.851	D	0.392	neutral	None	None	None	None	I
E/S	0.2662	likely_benign	0.2933	benign	0.163	Stabilizing	0.919	D	0.401	neutral	None	None	None	None	I
E/T	0.3068	likely_benign	0.3382	benign	0.258	Stabilizing	0.976	D	0.399	neutral	None	None	None	None	I
E/V	0.3457	ambiguous	0.3928	ambiguous	0.187	Stabilizing	0.984	D	0.438	neutral	N	0.517406686	None	None	I
E/W	0.9667	likely_pathogenic	0.978	pathogenic	-0.057	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
E/Y	0.8269	likely_pathogenic	0.8659	pathogenic	0.14	Stabilizing	0.996	D	0.53	neutral	None	None	None	None	I

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.