TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6389	19390;19391;19392	chr2:178728761;178728760;178728759	chr2:179593488;179593487;179593486
N2AB	6072	18439;18440;18441	chr2:178728761;178728760;178728759	chr2:179593488;179593487;179593486
N2A	5145	15658;15659;15660	chr2:178728761;178728760;178728759	chr2:179593488;179593487;179593486
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-48
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.476
• 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/Q	rs1256437537	0.021	0.983	D	0.589	0.223	0.350524144436	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/Q	rs1256437537	0.021	0.983	D	0.589	0.223	0.350524144436	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/Q	rs1256437537	0.021	0.983	D	0.589	0.223	0.350524144436	gnomAD-4.0.0	2.49858E-06	None	None	None	None	N	None	0	0	None	0	2.24588E-05	None	0	0	1.71006E-06	1.10514E-05	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	0.3121	likely_benign	0.2831	benign	-0.415	Destabilizing	0.892	D	0.597	neutral	N	0.502240102	None	None	N
E/C	0.9402	likely_pathogenic	0.9349	pathogenic	-0.153	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/D	0.2442	likely_benign	0.1964	benign	-0.453	Destabilizing	0.011	N	0.139	neutral	N	0.496670695	None	None	N
E/F	0.9074	likely_pathogenic	0.8889	pathogenic	-0.159	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
E/G	0.2952	likely_benign	0.2559	benign	-0.64	Destabilizing	0.892	D	0.539	neutral	N	0.514356876	None	None	N
E/H	0.6423	likely_pathogenic	0.5971	pathogenic	0.102	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/I	0.6782	likely_pathogenic	0.6265	pathogenic	0.151	Stabilizing	0.987	D	0.694	prob.neutral	None	None	None	None	N
E/K	0.2131	likely_benign	0.1938	benign	0.254	Stabilizing	0.892	D	0.549	neutral	N	0.514105637	None	None	N
E/L	0.6711	likely_pathogenic	0.6366	pathogenic	0.151	Stabilizing	0.987	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.7086	likely_pathogenic	0.6814	pathogenic	0.201	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/N	0.4698	ambiguous	0.39	ambiguous	-0.193	Destabilizing	0.95	D	0.608	neutral	None	None	None	None	N
E/P	0.9621	likely_pathogenic	0.9642	pathogenic	-0.017	Destabilizing	0.987	D	0.702	prob.neutral	None	None	None	None	N
E/Q	0.1665	likely_benign	0.154	benign	-0.132	Destabilizing	0.983	D	0.589	neutral	D	0.528090868	None	None	N
E/R	0.3508	ambiguous	0.3283	benign	0.53	Stabilizing	0.987	D	0.675	neutral	None	None	None	None	N
E/S	0.3456	ambiguous	0.2999	benign	-0.34	Destabilizing	0.916	D	0.553	neutral	None	None	None	None	N
E/T	0.3722	ambiguous	0.3204	benign	-0.152	Destabilizing	0.975	D	0.641	neutral	None	None	None	None	N
E/V	0.4305	ambiguous	0.3954	ambiguous	-0.017	Destabilizing	0.983	D	0.674	neutral	N	0.484237979	None	None	N
E/W	0.949	likely_pathogenic	0.9441	pathogenic	0.034	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
E/Y	0.8222	likely_pathogenic	0.7942	pathogenic	0.095	Stabilizing	0.999	D	0.655	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.