TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25884	77875;77876;77877	chr2:178568482;178568481;178568480	chr2:179433209;179433208;179433207
N2AB	24243	72952;72953;72954	chr2:178568482;178568481;178568480	chr2:179433209;179433208;179433207
N2A	23316	70171;70172;70173	chr2:178568482;178568481;178568480	chr2:179433209;179433208;179433207
N2B	16819	50680;50681;50682	chr2:178568482;178568481;178568480	chr2:179433209;179433208;179433207
Novex-1	16944	51055;51056;51057	chr2:178568482;178568481;178568480	chr2:179433209;179433208;179433207
Novex-2	17011	51256;51257;51258	chr2:178568482;178568481;178568480	chr2:179433209;179433208;179433207
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-136
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3546
• 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	rs748940985	-0.879	0.014	D	0.301	0.133	0.327686398923	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	1.41603E-04	None	0	0	None	0	None	0	0	0
E/D	rs748940985	-0.879	0.014	D	0.301	0.133	0.327686398923	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/D	rs748940985	-0.879	0.014	D	0.301	0.133	0.327686398923	gnomAD-4.0.0	3.09925E-06	None	None	None	None	N	None	0	8.34084E-05	None	0	0	None	0	0	0	0	0
E/K	rs747699837	-0.029	0.963	N	0.578	0.303	0.328222422547	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	2.83E-05	None	9.68E-05	0	None	3.27E-05	None	0	2.35E-05	0
E/K	rs747699837	-0.029	0.963	N	0.578	0.303	0.328222422547	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	2.07125E-04	0
E/K	rs747699837	-0.029	0.963	N	0.578	0.303	0.328222422547	gnomAD-4.0.0	2.10757E-05	None	None	None	None	N	None	0	1.66828E-05	None	3.37952E-05	0	None	0	0	2.20418E-05	4.39203E-05	3.20359E-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	0.1397	likely_benign	0.1375	benign	-1.096	Destabilizing	0.698	D	0.637	neutral	D	0.522613264	None	None	N
E/C	0.6976	likely_pathogenic	0.6911	pathogenic	-0.433	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
E/D	0.0994	likely_benign	0.1076	benign	-0.891	Destabilizing	0.014	N	0.301	neutral	D	0.523133339	None	None	N
E/F	0.5979	likely_pathogenic	0.5915	pathogenic	-0.621	Destabilizing	0.978	D	0.747	deleterious	None	None	None	None	N
E/G	0.1756	likely_benign	0.1741	benign	-1.422	Destabilizing	0.822	D	0.702	prob.neutral	N	0.515436967	None	None	N
E/H	0.2867	likely_benign	0.2801	benign	-0.777	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
E/I	0.2561	likely_benign	0.2505	benign	-0.208	Destabilizing	0.956	D	0.756	deleterious	None	None	None	None	N
E/K	0.1418	likely_benign	0.1375	benign	-0.281	Destabilizing	0.963	D	0.578	neutral	N	0.511876195	None	None	N
E/L	0.3004	likely_benign	0.2884	benign	-0.208	Destabilizing	0.915	D	0.721	prob.delet.	None	None	None	None	N
E/M	0.34	ambiguous	0.3259	benign	0.271	Stabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
E/N	0.152	likely_benign	0.1556	benign	-0.806	Destabilizing	0.915	D	0.639	neutral	None	None	None	None	N
E/P	0.7896	likely_pathogenic	0.8249	pathogenic	-0.485	Destabilizing	0.978	D	0.746	deleterious	None	None	None	None	N
E/Q	0.1087	likely_benign	0.1023	benign	-0.721	Destabilizing	0.976	D	0.617	neutral	D	0.529539236	None	None	N
E/R	0.2239	likely_benign	0.2162	benign	-0.076	Destabilizing	0.956	D	0.655	neutral	None	None	None	None	N
E/S	0.1355	likely_benign	0.1346	benign	-1.107	Destabilizing	0.754	D	0.556	neutral	None	None	None	None	N
E/T	0.1408	likely_benign	0.1324	benign	-0.819	Destabilizing	0.043	N	0.41	neutral	None	None	None	None	N
E/V	0.168	likely_benign	0.1663	benign	-0.485	Destabilizing	0.89	D	0.709	prob.delet.	N	0.48729308	None	None	N
E/W	0.823	likely_pathogenic	0.8116	pathogenic	-0.284	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
E/Y	0.4676	ambiguous	0.4649	ambiguous	-0.321	Destabilizing	0.993	D	0.756	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.