TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31995	96208;96209;96210	chr2:178544246;178544245;178544244	chr2:179408973;179408972;179408971
N2AB	30354	91285;91286;91287	chr2:178544246;178544245;178544244	chr2:179408973;179408972;179408971
N2A	29427	88504;88505;88506	chr2:178544246;178544245;178544244	chr2:179408973;179408972;179408971
N2B	22930	69013;69014;69015	chr2:178544246;178544245;178544244	chr2:179408973;179408972;179408971
Novex-1	23055	69388;69389;69390	chr2:178544246;178544245;178544244	chr2:179408973;179408972;179408971
Novex-2	23122	69589;69590;69591	chr2:178544246;178544245;178544244	chr2:179408973;179408972;179408971
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: Fn3-121
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.7301
• Predicted PPI site: I

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	rs776682000	0.549	0.739	N	0.673	0.285	0.305086939656	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	1.78E-05	0
E/K	rs776682000	0.549	0.739	N	0.673	0.285	0.305086939656	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs776682000	0.549	0.739	N	0.673	0.285	0.305086939656	gnomAD-4.0.0	1.67326E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.35622E-05	1.09789E-04	1.60128E-05

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	0.1392	likely_benign	0.1423	benign	-0.321	Destabilizing	0.334	N	0.69	prob.neutral	N	0.483944941	None	None	I
E/C	0.7195	likely_pathogenic	0.7535	pathogenic	-0.111	Destabilizing	0.982	D	0.759	deleterious	None	None	None	None	I
E/D	0.0761	likely_benign	0.0842	benign	-0.325	Destabilizing	0.001	N	0.237	neutral	N	0.4504298	None	None	I
E/F	0.7042	likely_pathogenic	0.7327	pathogenic	-0.123	Destabilizing	0.982	D	0.724	prob.delet.	None	None	None	None	I
E/G	0.1595	likely_benign	0.1585	benign	-0.512	Destabilizing	0.334	N	0.671	neutral	D	0.522385899	None	None	I
E/H	0.4366	ambiguous	0.4526	ambiguous	0.242	Stabilizing	0.947	D	0.7	prob.neutral	None	None	None	None	I
E/I	0.3342	likely_benign	0.3442	ambiguous	0.146	Stabilizing	0.826	D	0.741	deleterious	None	None	None	None	I
E/K	0.1678	likely_benign	0.1594	benign	0.395	Stabilizing	0.739	D	0.673	neutral	N	0.467687409	None	None	I
E/L	0.3747	ambiguous	0.3923	ambiguous	0.146	Stabilizing	0.7	D	0.736	prob.delet.	None	None	None	None	I
E/M	0.4407	ambiguous	0.4474	ambiguous	0.138	Stabilizing	0.982	D	0.731	prob.delet.	None	None	None	None	I
E/N	0.167	likely_benign	0.1804	benign	-0.023	Destabilizing	0.539	D	0.734	prob.delet.	None	None	None	None	I
E/P	0.3086	likely_benign	0.3549	ambiguous	0.01	Stabilizing	0.826	D	0.747	deleterious	None	None	None	None	I
E/Q	0.1617	likely_benign	0.1605	benign	0.031	Stabilizing	0.817	D	0.719	prob.delet.	N	0.460953438	None	None	I
E/R	0.2687	likely_benign	0.2689	benign	0.643	Stabilizing	0.7	D	0.749	deleterious	None	None	None	None	I
E/S	0.1531	likely_benign	0.1626	benign	-0.157	Destabilizing	0.25	N	0.679	prob.neutral	None	None	None	None	I
E/T	0.1937	likely_benign	0.2004	benign	0.01	Stabilizing	0.7	D	0.711	prob.delet.	None	None	None	None	I
E/V	0.2113	likely_benign	0.2165	benign	0.01	Stabilizing	0.781	D	0.735	prob.delet.	N	0.506533799	None	None	I
E/W	0.86	likely_pathogenic	0.8717	pathogenic	0.048	Stabilizing	0.982	D	0.747	deleterious	None	None	None	None	I
E/Y	0.5441	ambiguous	0.5661	pathogenic	0.131	Stabilizing	0.982	D	0.741	deleterious	None	None	None	None	I

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.