TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20591	61996;61997;61998	chr2:178589954;178589953;178589952	chr2:179454681;179454680;179454679
N2AB	18950	57073;57074;57075	chr2:178589954;178589953;178589952	chr2:179454681;179454680;179454679
N2A	18023	54292;54293;54294	chr2:178589954;178589953;178589952	chr2:179454681;179454680;179454679
N2B	11526	34801;34802;34803	chr2:178589954;178589953;178589952	chr2:179454681;179454680;179454679
Novex-1	11651	35176;35177;35178	chr2:178589954;178589953;178589952	chr2:179454681;179454680;179454679
Novex-2	11718	35377;35378;35379	chr2:178589954;178589953;178589952	chr2:179454681;179454680;179454679
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: Fn3-37
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4001
• 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/K	rs1327237859	-0.777	0.978	N	0.492	0.382	0.330331372229	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1327237859	-0.777	0.978	N	0.492	0.382	0.330331372229	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.4208	ambiguous	0.4419	ambiguous	-0.657	Destabilizing	0.989	D	0.641	neutral	N	0.505437721	None	None	N
E/C	0.9471	likely_pathogenic	0.9494	pathogenic	-0.321	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/D	0.1463	likely_benign	0.1619	benign	-1.028	Destabilizing	0.054	N	0.167	neutral	N	0.452584671	None	None	N
E/F	0.9537	likely_pathogenic	0.9529	pathogenic	-0.462	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/G	0.3736	ambiguous	0.3849	ambiguous	-0.966	Destabilizing	0.978	D	0.675	neutral	N	0.516636149	None	None	N
E/H	0.8371	likely_pathogenic	0.8443	pathogenic	-0.752	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
E/I	0.7863	likely_pathogenic	0.7949	pathogenic	0.162	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
E/K	0.5433	ambiguous	0.5456	ambiguous	-0.583	Destabilizing	0.978	D	0.492	neutral	N	0.4752481	None	None	N
E/L	0.8012	likely_pathogenic	0.8076	pathogenic	0.162	Stabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
E/M	0.814	likely_pathogenic	0.8136	pathogenic	0.552	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.4265	ambiguous	0.4418	ambiguous	-0.835	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
E/P	0.9826	likely_pathogenic	0.9862	pathogenic	-0.089	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/Q	0.3466	ambiguous	0.3561	ambiguous	-0.745	Destabilizing	0.997	D	0.601	neutral	N	0.495412728	None	None	N
E/R	0.7103	likely_pathogenic	0.7127	pathogenic	-0.371	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
E/S	0.4187	ambiguous	0.4439	ambiguous	-1.099	Destabilizing	0.983	D	0.516	neutral	None	None	None	None	N
E/T	0.5308	ambiguous	0.5555	ambiguous	-0.862	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/V	0.5822	likely_pathogenic	0.597	pathogenic	-0.089	Destabilizing	0.999	D	0.761	deleterious	N	0.468979382	None	None	N
E/W	0.9829	likely_pathogenic	0.9811	pathogenic	-0.352	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/Y	0.8976	likely_pathogenic	0.8971	pathogenic	-0.263	Destabilizing	1.0	D	0.771	deleterious	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.