TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27930	84013;84014;84015	chr2:178562344;178562343;178562342	chr2:179427071;179427070;179427069
N2AB	26289	79090;79091;79092	chr2:178562344;178562343;178562342	chr2:179427071;179427070;179427069
N2A	25362	76309;76310;76311	chr2:178562344;178562343;178562342	chr2:179427071;179427070;179427069
N2B	18865	56818;56819;56820	chr2:178562344;178562343;178562342	chr2:179427071;179427070;179427069
Novex-1	18990	57193;57194;57195	chr2:178562344;178562343;178562342	chr2:179427071;179427070;179427069
Novex-2	19057	57394;57395;57396	chr2:178562344;178562343;178562342	chr2:179427071;179427070;179427069
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: Fn3-91
• Domain position: 68
• Structural Position: 102
• Q(SASA): 0.1527
• 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	rs901577328	None	0.91	N	0.601	0.396	None	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	rs901577328	None	0.91	N	0.601	0.396	None	gnomAD-4.0.0	6.57134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46994E-05	0	0
E/K	rs1225134445	-0.758	0.919	N	0.477	0.32	0.279370189704	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
E/K	rs1225134445	-0.758	0.919	N	0.477	0.32	0.279370189704	gnomAD-4.0.0	9.58797E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89222E-05	0	1.43303E-05	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	0.2102	likely_benign	0.2323	benign	-0.917	Destabilizing	0.859	D	0.564	neutral	N	0.482192715	None	None	N
E/C	0.8757	likely_pathogenic	0.8962	pathogenic	-0.462	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
E/D	0.21	likely_benign	0.2387	benign	-0.977	Destabilizing	0.14	N	0.481	neutral	N	0.514729208	None	None	N
E/F	0.8476	likely_pathogenic	0.8801	pathogenic	-0.273	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
E/G	0.2119	likely_benign	0.2282	benign	-1.279	Destabilizing	0.91	D	0.601	neutral	N	0.482483503	None	None	N
E/H	0.5828	likely_pathogenic	0.6341	pathogenic	-0.464	Destabilizing	0.987	D	0.664	neutral	None	None	None	None	N
E/I	0.4956	ambiguous	0.5616	ambiguous	0.069	Stabilizing	0.98	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.1763	likely_benign	0.2047	benign	-0.563	Destabilizing	0.919	D	0.477	neutral	N	0.454256752	None	None	N
E/L	0.5303	ambiguous	0.5902	pathogenic	0.069	Stabilizing	0.98	D	0.73	prob.delet.	None	None	None	None	N
E/M	0.4906	ambiguous	0.5401	ambiguous	0.487	Stabilizing	0.99	D	0.673	neutral	None	None	None	None	N
E/N	0.3237	likely_benign	0.3666	ambiguous	-1.068	Destabilizing	0.023	N	0.298	neutral	None	None	None	None	N
E/P	0.9604	likely_pathogenic	0.9697	pathogenic	-0.239	Destabilizing	0.958	D	0.641	neutral	None	None	None	None	N
E/Q	0.1449	likely_benign	0.156	benign	-0.932	Destabilizing	0.966	D	0.659	neutral	N	0.464473746	None	None	N
E/R	0.3221	likely_benign	0.3683	ambiguous	-0.23	Destabilizing	0.981	D	0.675	neutral	None	None	None	None	N
E/S	0.2483	likely_benign	0.2768	benign	-1.369	Destabilizing	0.802	D	0.49	neutral	None	None	None	None	N
E/T	0.2655	likely_benign	0.3112	benign	-1.068	Destabilizing	0.975	D	0.645	neutral	None	None	None	None	N
E/V	0.2944	likely_benign	0.3316	benign	-0.239	Destabilizing	0.964	D	0.684	prob.neutral	N	0.466724617	None	None	N
E/W	0.9492	likely_pathogenic	0.9652	pathogenic	0.033	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/Y	0.7456	likely_pathogenic	0.7938	pathogenic	-0.01	Destabilizing	0.999	D	0.699	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.