TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14533	43822;43823;43824	chr2:178632297;178632296;178632295	chr2:179497024;179497023;179497022
N2AB	12892	38899;38900;38901	chr2:178632297;178632296;178632295	chr2:179497024;179497023;179497022
N2A	11965	36118;36119;36120	chr2:178632297;178632296;178632295	chr2:179497024;179497023;179497022
N2B	5468	16627;16628;16629	chr2:178632297;178632296;178632295	chr2:179497024;179497023;179497022
Novex-1	5593	17002;17003;17004	chr2:178632297;178632296;178632295	chr2:179497024;179497023;179497022
Novex-2	5660	17203;17204;17205	chr2:178632297;178632296;178632295	chr2:179497024;179497023;179497022
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-96
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.7543
• 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
D/E	None	None	0.008	N	0.166	0.326	0.257786959452	gnomAD-4.0.0	1.37225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80198E-06	0	0
D/G	None	None	0.722	N	0.401	0.471	0.292062946507	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.3263	likely_benign	0.3154	benign	-0.22	Destabilizing	0.565	D	0.427	neutral	D	0.629555759	None	None	N
D/C	0.7652	likely_pathogenic	0.7514	pathogenic	-0.139	Destabilizing	0.996	D	0.636	neutral	None	None	None	None	N
D/E	0.2316	likely_benign	0.2216	benign	-0.245	Destabilizing	0.008	N	0.166	neutral	N	0.511305053	None	None	N
D/F	0.7095	likely_pathogenic	0.713	pathogenic	0.016	Stabilizing	0.987	D	0.571	neutral	None	None	None	None	N
D/G	0.1526	likely_benign	0.1398	benign	-0.444	Destabilizing	0.722	D	0.401	neutral	N	0.483669246	None	None	N
D/H	0.3564	ambiguous	0.3451	ambiguous	0.237	Stabilizing	0.949	D	0.433	neutral	D	0.628361825	None	None	N
D/I	0.5836	likely_pathogenic	0.5965	pathogenic	0.33	Stabilizing	0.961	D	0.572	neutral	None	None	None	None	N
D/K	0.4432	ambiguous	0.434	ambiguous	0.192	Stabilizing	0.633	D	0.401	neutral	None	None	None	None	N
D/L	0.59	likely_pathogenic	0.5883	pathogenic	0.33	Stabilizing	0.923	D	0.551	neutral	None	None	None	None	N
D/M	0.7954	likely_pathogenic	0.7941	pathogenic	0.318	Stabilizing	0.996	D	0.575	neutral	None	None	None	None	N
D/N	0.1058	likely_benign	0.0972	benign	-0.161	Destabilizing	0.075	N	0.267	neutral	D	0.590157361	None	None	N
D/P	0.8886	likely_pathogenic	0.8815	pathogenic	0.169	Stabilizing	0.961	D	0.434	neutral	None	None	None	None	N
D/Q	0.4367	ambiguous	0.4148	ambiguous	-0.088	Destabilizing	0.237	N	0.316	neutral	None	None	None	None	N
D/R	0.4461	ambiguous	0.4533	ambiguous	0.46	Stabilizing	0.923	D	0.467	neutral	None	None	None	None	N
D/S	0.1614	likely_benign	0.1466	benign	-0.292	Destabilizing	0.633	D	0.397	neutral	None	None	None	None	N
D/T	0.4146	ambiguous	0.3904	ambiguous	-0.11	Destabilizing	0.775	D	0.401	neutral	None	None	None	None	N
D/V	0.4185	ambiguous	0.4469	ambiguous	0.169	Stabilizing	0.901	D	0.557	neutral	D	0.62824211	None	None	N
D/W	0.9191	likely_pathogenic	0.93	pathogenic	0.173	Stabilizing	0.996	D	0.649	neutral	None	None	None	None	N
D/Y	0.2951	likely_benign	0.302	benign	0.259	Stabilizing	0.983	D	0.577	neutral	D	0.62846842	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.