TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5982	18169;18170;18171	chr2:178730589;178730588;178730587	chr2:179595316;179595315;179595314
N2AB	5665	17218;17219;17220	chr2:178730589;178730588;178730587	chr2:179595316;179595315;179595314
N2A	4738	14437;14438;14439	chr2:178730589;178730588;178730587	chr2:179595316;179595315;179595314
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-43
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.4459
• 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/D	rs760854297	-0.339	0.031	N	0.159	0.11	0.279370189704	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs760854297	-0.339	0.031	N	0.159	0.11	0.279370189704	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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	0.1572	likely_benign	0.1602	benign	-0.651	Destabilizing	0.98	D	0.357	neutral	D	0.522554549	None	None	N
E/C	0.8483	likely_pathogenic	0.8572	pathogenic	-0.142	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	N
E/D	0.1212	likely_benign	0.1297	benign	-0.509	Destabilizing	0.031	N	0.159	neutral	N	0.445960635	None	None	N
E/F	0.7788	likely_pathogenic	0.7991	pathogenic	-0.375	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
E/G	0.1761	likely_benign	0.2016	benign	-0.904	Destabilizing	0.961	D	0.381	neutral	D	0.528808518	None	None	N
E/H	0.4232	ambiguous	0.4228	ambiguous	-0.331	Destabilizing	0.996	D	0.37	neutral	None	None	None	None	N
E/I	0.4391	ambiguous	0.4665	ambiguous	0.004	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
E/K	0.1971	likely_benign	0.2	benign	0.073	Stabilizing	0.961	D	0.377	neutral	N	0.50033105	None	None	N
E/L	0.3859	ambiguous	0.4006	ambiguous	0.004	Stabilizing	0.996	D	0.449	neutral	None	None	None	None	N
E/M	0.5071	ambiguous	0.5151	ambiguous	0.284	Stabilizing	1.0	D	0.498	neutral	None	None	None	None	N
E/N	0.246	likely_benign	0.2564	benign	-0.341	Destabilizing	0.304	N	0.237	neutral	None	None	None	None	N
E/P	0.8963	likely_pathogenic	0.9235	pathogenic	-0.193	Destabilizing	0.999	D	0.36	neutral	None	None	None	None	N
E/Q	0.1325	likely_benign	0.127	benign	-0.276	Destabilizing	0.98	D	0.401	neutral	N	0.460812657	None	None	N
E/R	0.2947	likely_benign	0.3029	benign	0.295	Stabilizing	0.996	D	0.366	neutral	None	None	None	None	N
E/S	0.1724	likely_benign	0.1853	benign	-0.539	Destabilizing	0.97	D	0.337	neutral	None	None	None	None	N
E/T	0.2034	likely_benign	0.2077	benign	-0.328	Destabilizing	0.97	D	0.389	neutral	None	None	None	None	N
E/V	0.2381	likely_benign	0.2523	benign	-0.193	Destabilizing	0.998	D	0.413	neutral	N	0.511108191	None	None	N
E/W	0.9053	likely_pathogenic	0.9183	pathogenic	-0.15	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/Y	0.6734	likely_pathogenic	0.698	pathogenic	-0.121	Destabilizing	0.999	D	0.501	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.