TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28400	85423;85424;85425	chr2:178560934;178560933;178560932	chr2:179425661;179425660;179425659
N2AB	26759	80500;80501;80502	chr2:178560934;178560933;178560932	chr2:179425661;179425660;179425659
N2A	25832	77719;77720;77721	chr2:178560934;178560933;178560932	chr2:179425661;179425660;179425659
N2B	19335	58228;58229;58230	chr2:178560934;178560933;178560932	chr2:179425661;179425660;179425659
Novex-1	19460	58603;58604;58605	chr2:178560934;178560933;178560932	chr2:179425661;179425660;179425659
Novex-2	19527	58804;58805;58806	chr2:178560934;178560933;178560932	chr2:179425661;179425660;179425659
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-143
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.432
• 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/G	rs1179703111	-0.678	0.003	N	0.199	0.156	0.401753679984	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/G	rs1179703111	-0.678	0.003	N	0.199	0.156	0.401753679984	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1179703111	-0.678	0.003	N	0.199	0.156	0.401753679984	gnomAD-4.0.0	1.85904E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69516E-06	0	1.60108E-05

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	0.1366	likely_benign	0.129	benign	-0.351	Destabilizing	0.012	N	0.16	neutral	N	0.477494263	None	None	N
E/C	0.7952	likely_pathogenic	0.7857	pathogenic	-0.187	Destabilizing	0.996	D	0.367	neutral	None	None	None	None	N
E/D	0.1543	likely_benign	0.1477	benign	-0.386	Destabilizing	0.472	N	0.299	neutral	N	0.480342567	None	None	N
E/F	0.7352	likely_pathogenic	0.7297	pathogenic	-0.127	Destabilizing	0.984	D	0.361	neutral	None	None	None	None	N
E/G	0.1099	likely_benign	0.103	benign	-0.566	Destabilizing	0.003	N	0.199	neutral	N	0.521535829	None	None	N
E/H	0.4668	ambiguous	0.4411	ambiguous	0.128	Stabilizing	0.953	D	0.323	neutral	None	None	None	None	N
E/I	0.3738	ambiguous	0.351	ambiguous	0.188	Stabilizing	0.953	D	0.379	neutral	None	None	None	None	N
E/K	0.122	likely_benign	0.1067	benign	0.199	Stabilizing	0.521	D	0.301	neutral	N	0.486113746	None	None	N
E/L	0.3673	ambiguous	0.3418	ambiguous	0.188	Stabilizing	0.742	D	0.371	neutral	None	None	None	None	N
E/M	0.4486	ambiguous	0.4274	ambiguous	0.175	Stabilizing	0.987	D	0.342	neutral	None	None	None	None	N
E/N	0.2454	likely_benign	0.2347	benign	-0.164	Destabilizing	0.742	D	0.289	neutral	None	None	None	None	N
E/P	0.2884	likely_benign	0.2741	benign	0.029	Stabilizing	0.953	D	0.329	neutral	None	None	None	None	N
E/Q	0.1391	likely_benign	0.1248	benign	-0.108	Destabilizing	0.028	N	0.177	neutral	N	0.486921823	None	None	N
E/R	0.2167	likely_benign	0.1948	benign	0.471	Stabilizing	0.59	D	0.286	neutral	None	None	None	None	N
E/S	0.1861	likely_benign	0.1831	benign	-0.327	Destabilizing	0.373	N	0.304	neutral	None	None	None	None	N
E/T	0.2044	likely_benign	0.1996	benign	-0.151	Destabilizing	0.742	D	0.331	neutral	None	None	None	None	N
E/V	0.21	likely_benign	0.1981	benign	0.029	Stabilizing	0.684	D	0.353	neutral	D	0.529981954	None	None	N
E/W	0.8564	likely_pathogenic	0.8351	pathogenic	0.037	Stabilizing	0.996	D	0.391	neutral	None	None	None	None	N
E/Y	0.5783	likely_pathogenic	0.5586	ambiguous	0.114	Stabilizing	0.984	D	0.349	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.