TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16243	48952;48953;48954	chr2:178614880;178614879;178614878	chr2:179479607;179479606;179479605
N2AB	14602	44029;44030;44031	chr2:178614880;178614879;178614878	chr2:179479607;179479606;179479605
N2A	13675	41248;41249;41250	chr2:178614880;178614879;178614878	chr2:179479607;179479606;179479605
N2B	7178	21757;21758;21759	chr2:178614880;178614879;178614878	chr2:179479607;179479606;179479605
Novex-1	7303	22132;22133;22134	chr2:178614880;178614879;178614878	chr2:179479607;179479606;179479605
Novex-2	7370	22333;22334;22335	chr2:178614880;178614879;178614878	chr2:179479607;179479606;179479605
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-5
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.5805
• 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
P/A	rs72677242	None	0.06	N	0.311	0.278	0.15556083564	gnomAD-4.0.0	1.40451E-06	None	None	None	None	N	None	3.04414E-05	0	None	0	0	None	0	0	9.16288E-07	0	0
P/H	rs1176398842	None	0.999	D	0.763	0.284	0.465633601861	gnomAD-4.0.0	7.02463E-07	None	None	None	None	N	None	0	0	None	0	2.63685E-05	None	0	0	0	0	0
P/L	rs1176398842	-0.132	0.919	N	0.674	0.291	0.518312163451	gnomAD-2.1.1	8.96E-06	None	None	None	None	N	None	4.9E-05	0	None	0	0	None	0	None	0	1.04E-05	0
P/L	rs1176398842	-0.132	0.919	N	0.674	0.291	0.518312163451	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	1.95695E-04	None	0	0	0	0	0
P/L	rs1176398842	-0.132	0.919	N	0.674	0.291	0.518312163451	gnomAD-4.0.0	6.3479E-06	None	None	None	None	N	None	0	0	None	0	2.32374E-05	None	0	0	6.90228E-06	0	1.63698E-05
P/S	rs72677242	-0.517	0.307	N	0.333	0.203	None	gnomAD-2.1.1	3.79376E-03	None	None	None	None	N	None	1.46513E-04	4.57167E-04	None	1.80582E-03	0	None	5.12013E-04	None	1.52761E-02	4.67743E-03	2.10902E-03
P/S	rs72677242	-0.517	0.307	N	0.333	0.203	None	gnomAD-3.1.2	3.10817E-03	None	None	None	None	N	None	4.83E-05	1.97031E-04	0	2.01845E-03	0	None	1.5867E-02	3.16456E-03	4.15292E-03	1.03691E-03	1.91205E-03
P/S	rs72677242	-0.517	0.307	N	0.333	0.203	None	1000 genomes	1.59744E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	6E-03	None	None	None	1E-03	None
P/S	rs72677242	-0.517	0.307	N	0.333	0.203	None	gnomAD-4.0.0	2.45184E-03	None	None	None	None	N	None	4.03356E-05	4.27748E-04	None	1.24258E-03	0	None	1.54746E-02	3.33444E-04	2.30838E-03	5.89146E-04	1.88111E-03
P/T	None	-0.517	0.851	N	0.503	0.233	None	gnomAD-2.1.1	3.63E-05	None	None	None	None	N	None	0	3.62E-05	None	0	0	None	0	None	0	7.37E-05	0
P/T	None	-0.517	0.851	N	0.503	0.233	None	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.42E-05	0	0
P/T	None	-0.517	0.851	N	0.503	0.233	None	gnomAD-4.0.0	1.04071E-04	None	None	None	None	N	None	0	1.86047E-05	None	0	0	None	0	0	1.39744E-04	0	1.63634E-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
P/A	0.0791	likely_benign	0.0883	benign	-1.022	Destabilizing	0.06	N	0.311	neutral	N	0.442072535	None	None	N
P/C	0.5953	likely_pathogenic	0.6062	pathogenic	-0.667	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
P/D	0.8008	likely_pathogenic	0.8329	pathogenic	-0.451	Destabilizing	0.938	D	0.544	neutral	None	None	None	None	N
P/E	0.5528	ambiguous	0.6136	pathogenic	-0.486	Destabilizing	0.938	D	0.513	neutral	None	None	None	None	N
P/F	0.7291	likely_pathogenic	0.7747	pathogenic	-0.844	Destabilizing	0.997	D	0.803	deleterious	None	None	None	None	N
P/G	0.4967	ambiguous	0.533	ambiguous	-1.278	Destabilizing	0.938	D	0.605	neutral	None	None	None	None	N
P/H	0.5463	ambiguous	0.5877	pathogenic	-0.752	Destabilizing	0.999	D	0.763	deleterious	D	0.530081978	None	None	N
P/I	0.3612	ambiguous	0.4436	ambiguous	-0.447	Destabilizing	0.991	D	0.751	deleterious	None	None	None	None	N
P/K	0.7065	likely_pathogenic	0.7286	pathogenic	-0.76	Destabilizing	0.938	D	0.52	neutral	None	None	None	None	N
P/L	0.2295	likely_benign	0.2814	benign	-0.447	Destabilizing	0.919	D	0.674	prob.neutral	N	0.473998774	None	None	N
P/M	0.4051	ambiguous	0.4753	ambiguous	-0.409	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
P/N	0.6091	likely_pathogenic	0.6977	pathogenic	-0.512	Destabilizing	0.981	D	0.669	prob.neutral	None	None	None	None	N
P/Q	0.3708	ambiguous	0.4201	ambiguous	-0.676	Destabilizing	0.991	D	0.602	neutral	None	None	None	None	N
P/R	0.599	likely_pathogenic	0.6031	pathogenic	-0.281	Destabilizing	0.988	D	0.718	prob.delet.	D	0.559230561	None	None	N
P/S	0.2322	likely_benign	0.2564	benign	-1.016	Destabilizing	0.307	N	0.333	neutral	N	0.471004915	None	None	N
P/T	0.1896	likely_benign	0.2145	benign	-0.937	Destabilizing	0.851	D	0.503	neutral	N	0.474981688	None	None	N
P/V	0.2279	likely_benign	0.2745	benign	-0.602	Destabilizing	0.938	D	0.603	neutral	None	None	None	None	N
P/W	0.8986	likely_pathogenic	0.9131	pathogenic	-0.977	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
P/Y	0.7432	likely_pathogenic	0.784	pathogenic	-0.679	Destabilizing	0.997	D	0.801	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.