TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9285	28078;28079;28080	chr2:178711977;178711976;178711975	chr2:179576704;179576703;179576702
N2AB	8968	27127;27128;27129	chr2:178711977;178711976;178711975	chr2:179576704;179576703;179576702
N2A	8041	24346;24347;24348	chr2:178711977;178711976;178711975	chr2:179576704;179576703;179576702
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-78
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5286
• 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	rs1560573999	None	0.007	N	0.225	0.248	0.297718772494	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/A	rs1560573999	None	0.007	N	0.225	0.248	0.297718772494	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs1560573999	None	0.007	N	0.225	0.248	0.297718772494	gnomAD-4.0.0	6.5722E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4699E-05	0	0
E/K	None	None	0.549	N	0.391	0.215	0.283761946502	gnomAD-4.0.0	1.60823E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8929E-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	0.1243	likely_benign	0.1379	benign	-0.482	Destabilizing	0.007	N	0.225	neutral	N	0.465509187	None	None	I
E/C	0.7928	likely_pathogenic	0.8015	pathogenic	-0.171	Destabilizing	0.992	D	0.559	neutral	None	None	None	None	I
E/D	0.1676	likely_benign	0.1735	benign	-0.444	Destabilizing	0.004	N	0.141	neutral	N	0.484076306	None	None	I
E/F	0.6321	likely_pathogenic	0.6413	pathogenic	-0.245	Destabilizing	0.972	D	0.562	neutral	None	None	None	None	I
E/G	0.1747	likely_benign	0.2094	benign	-0.7	Destabilizing	0.334	N	0.548	neutral	D	0.53631328	None	None	I
E/H	0.3874	ambiguous	0.4226	ambiguous	-0.007	Destabilizing	0.972	D	0.469	neutral	None	None	None	None	I
E/I	0.3024	likely_benign	0.3363	benign	0.065	Stabilizing	0.92	D	0.562	neutral	None	None	None	None	I
E/K	0.114	likely_benign	0.1488	benign	0.233	Stabilizing	0.549	D	0.391	neutral	N	0.452057101	None	None	I
E/L	0.378	ambiguous	0.4208	ambiguous	0.065	Stabilizing	0.617	D	0.575	neutral	None	None	None	None	I
E/M	0.351	ambiguous	0.383	ambiguous	0.15	Stabilizing	0.992	D	0.547	neutral	None	None	None	None	I
E/N	0.234	likely_benign	0.2545	benign	-0.167	Destabilizing	0.447	N	0.397	neutral	None	None	None	None	I
E/P	0.8838	likely_pathogenic	0.8967	pathogenic	-0.097	Destabilizing	0.92	D	0.489	neutral	None	None	None	None	I
E/Q	0.1146	likely_benign	0.1282	benign	-0.128	Destabilizing	0.549	D	0.463	neutral	N	0.485652386	None	None	I
E/R	0.2113	likely_benign	0.2537	benign	0.498	Stabilizing	0.92	D	0.435	neutral	None	None	None	None	I
E/S	0.152	likely_benign	0.1548	benign	-0.336	Destabilizing	0.026	N	0.133	neutral	None	None	None	None	I
E/T	0.1607	likely_benign	0.1681	benign	-0.155	Destabilizing	0.447	N	0.473	neutral	None	None	None	None	I
E/V	0.1802	likely_benign	0.1977	benign	-0.097	Destabilizing	0.549	D	0.565	neutral	N	0.50102727	None	None	I
E/W	0.8559	likely_pathogenic	0.8783	pathogenic	-0.041	Destabilizing	0.992	D	0.621	neutral	None	None	None	None	I
E/Y	0.545	ambiguous	0.5738	pathogenic	0.013	Stabilizing	0.972	D	0.557	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.