TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20758	62497;62498;62499	chr2:178589453;178589452;178589451	chr2:179454180;179454179;179454178
N2AB	19117	57574;57575;57576	chr2:178589453;178589452;178589451	chr2:179454180;179454179;179454178
N2A	18190	54793;54794;54795	chr2:178589453;178589452;178589451	chr2:179454180;179454179;179454178
N2B	11693	35302;35303;35304	chr2:178589453;178589452;178589451	chr2:179454180;179454179;179454178
Novex-1	11818	35677;35678;35679	chr2:178589453;178589452;178589451	chr2:179454180;179454179;179454178
Novex-2	11885	35878;35879;35880	chr2:178589453;178589452;178589451	chr2:179454180;179454179;179454178
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: Fn3-38
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.8121
• 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/K	rs794729470	None	0.039	N	0.253	0.124	None	gnomAD-4.0.0	7.5279E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.89502E-06	0	0
E/V	None	None	0.047	N	0.425	0.182	0.281381271821	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	0.1245	likely_benign	0.1244	benign	-0.054	Destabilizing	None	N	0.09	neutral	N	0.403670429	None	None	I
E/C	0.7898	likely_pathogenic	0.8189	pathogenic	-0.195	Destabilizing	0.914	D	0.353	neutral	None	None	None	None	I
E/D	0.1068	likely_benign	0.1188	benign	-0.17	Destabilizing	None	N	0.066	neutral	N	0.412868702	None	None	I
E/F	0.8027	likely_pathogenic	0.8446	pathogenic	-0.065	Destabilizing	0.482	N	0.491	neutral	None	None	None	None	I
E/G	0.1428	likely_benign	0.1144	benign	-0.182	Destabilizing	None	N	0.157	neutral	N	0.453368531	None	None	I
E/H	0.4671	ambiguous	0.5081	ambiguous	0.521	Stabilizing	0.739	D	0.293	neutral	None	None	None	None	I
E/I	0.4306	ambiguous	0.5099	ambiguous	0.227	Stabilizing	0.116	N	0.541	neutral	None	None	None	None	I
E/K	0.141	likely_benign	0.1868	benign	0.359	Stabilizing	0.039	N	0.253	neutral	N	0.396821814	None	None	I
E/L	0.4281	ambiguous	0.4807	ambiguous	0.227	Stabilizing	0.116	N	0.476	neutral	None	None	None	None	I
E/M	0.4782	ambiguous	0.5468	ambiguous	0.002	Stabilizing	0.739	D	0.407	neutral	None	None	None	None	I
E/N	0.205	likely_benign	0.2258	benign	0.182	Stabilizing	0.051	N	0.21	neutral	None	None	None	None	I
E/P	0.3248	likely_benign	0.3092	benign	0.152	Stabilizing	0.209	N	0.448	neutral	None	None	None	None	I
E/Q	0.1451	likely_benign	0.1587	benign	0.194	Stabilizing	0.167	N	0.351	neutral	N	0.471780933	None	None	I
E/R	0.249	likely_benign	0.2956	benign	0.623	Stabilizing	0.116	N	0.273	neutral	None	None	None	None	I
E/S	0.1514	likely_benign	0.1505	benign	-0.003	Destabilizing	None	N	0.074	neutral	None	None	None	None	I
E/T	0.1824	likely_benign	0.191	benign	0.106	Stabilizing	0.026	N	0.3	neutral	None	None	None	None	I
E/V	0.2582	likely_benign	0.3094	benign	0.152	Stabilizing	0.047	N	0.425	neutral	N	0.415442074	None	None	I
E/W	0.8957	likely_pathogenic	0.9155	pathogenic	-0.006	Destabilizing	0.914	D	0.325	neutral	None	None	None	None	I
E/Y	0.667	likely_pathogenic	0.7497	pathogenic	0.161	Stabilizing	0.739	D	0.484	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.