TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17587	52984;52985;52986	chr2:178608028;178608027;178608026	chr2:179472755;179472754;179472753
N2AB	15946	48061;48062;48063	chr2:178608028;178608027;178608026	chr2:179472755;179472754;179472753
N2A	15019	45280;45281;45282	chr2:178608028;178608027;178608026	chr2:179472755;179472754;179472753
N2B	8522	25789;25790;25791	chr2:178608028;178608027;178608026	chr2:179472755;179472754;179472753
Novex-1	8647	26164;26165;26166	chr2:178608028;178608027;178608026	chr2:179472755;179472754;179472753
Novex-2	8714	26365;26366;26367	chr2:178608028;178608027;178608026	chr2:179472755;179472754;179472753
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: Fn3-16
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1659
• 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	rs1271096467	-1.146	0.22	N	0.421	0.239	0.222439326576	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs1271096467	-1.146	0.22	N	0.421	0.239	0.222439326576	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1271096467	-1.146	0.22	N	0.421	0.239	0.222439326576	gnomAD-4.0.0	6.58068E-06	None	None	None	None	N	None	2.41476E-05	0	None	0	0	None	0	0	0	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	0.1423	likely_benign	0.1263	benign	-0.387	Destabilizing	0.22	N	0.475	neutral	N	0.422531122	None	None	N
E/C	0.7557	likely_pathogenic	0.7107	pathogenic	-0.128	Destabilizing	0.968	D	0.722	prob.delet.	None	None	None	None	N
E/D	0.1441	likely_benign	0.1137	benign	-1.097	Destabilizing	None	N	0.215	neutral	N	0.376721475	None	None	N
E/F	0.6737	likely_pathogenic	0.6207	pathogenic	-0.605	Destabilizing	0.89	D	0.739	prob.delet.	None	None	None	None	N
E/G	0.21	likely_benign	0.1837	benign	-0.683	Destabilizing	0.22	N	0.541	neutral	N	0.463801742	None	None	N
E/H	0.3987	ambiguous	0.3471	ambiguous	-0.99	Destabilizing	0.726	D	0.513	neutral	None	None	None	None	N
E/I	0.294	likely_benign	0.2658	benign	0.387	Stabilizing	0.726	D	0.747	deleterious	None	None	None	None	N
E/K	0.1749	likely_benign	0.1539	benign	-0.201	Destabilizing	0.22	N	0.421	neutral	N	0.422531122	None	None	N
E/L	0.3108	likely_benign	0.2869	benign	0.387	Stabilizing	0.567	D	0.695	prob.neutral	None	None	None	None	N
E/M	0.38	ambiguous	0.3502	ambiguous	0.788	Stabilizing	0.968	D	0.691	prob.neutral	None	None	None	None	N
E/N	0.2438	likely_benign	0.1918	benign	-0.445	Destabilizing	0.157	N	0.413	neutral	None	None	None	None	N
E/P	0.916	likely_pathogenic	0.9087	pathogenic	0.152	Stabilizing	0.726	D	0.579	neutral	None	None	None	None	N
E/Q	0.131	likely_benign	0.1182	benign	-0.382	Destabilizing	0.22	N	0.449	neutral	N	0.42651279	None	None	N
E/R	0.2772	likely_benign	0.2474	benign	-0.265	Destabilizing	0.567	D	0.487	neutral	None	None	None	None	N
E/S	0.1667	likely_benign	0.1452	benign	-0.736	Destabilizing	0.157	N	0.417	neutral	None	None	None	None	N
E/T	0.1513	likely_benign	0.136	benign	-0.491	Destabilizing	0.272	N	0.503	neutral	None	None	None	None	N
E/V	0.1776	likely_benign	0.164	benign	0.152	Stabilizing	0.667	D	0.612	neutral	N	0.393400294	None	None	N
E/W	0.8808	likely_pathogenic	0.8514	pathogenic	-0.659	Destabilizing	0.968	D	0.694	prob.neutral	None	None	None	None	N
E/Y	0.5814	likely_pathogenic	0.5256	ambiguous	-0.391	Destabilizing	0.89	D	0.691	prob.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.