TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25642	77149;77150;77151	chr2:178569208;178569207;178569206	chr2:179433935;179433934;179433933
N2AB	24001	72226;72227;72228	chr2:178569208;178569207;178569206	chr2:179433935;179433934;179433933
N2A	23074	69445;69446;69447	chr2:178569208;178569207;178569206	chr2:179433935;179433934;179433933
N2B	16577	49954;49955;49956	chr2:178569208;178569207;178569206	chr2:179433935;179433934;179433933
Novex-1	16702	50329;50330;50331	chr2:178569208;178569207;178569206	chr2:179433935;179433934;179433933
Novex-2	16769	50530;50531;50532	chr2:178569208;178569207;178569206	chr2:179433935;179433934;179433933
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: Fn3-74
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.1578
• 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/K	rs1455903337	-0.891	0.065	N	0.331	0.271	0.32306181527	gnomAD-4.0.0	1.6038E-06	None	None	None	None	N	None	0	0	None	0	2.77639E-05	None	0	0	0	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	0.8133	likely_pathogenic	0.8207	pathogenic	-0.998	Destabilizing	0.856	D	0.498	neutral	N	0.493146797	None	None	N
E/C	0.9933	likely_pathogenic	0.9929	pathogenic	-0.511	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/D	0.5268	ambiguous	0.5475	ambiguous	-1.062	Destabilizing	0.005	N	0.324	neutral	N	0.465225894	None	None	N
E/F	0.9939	likely_pathogenic	0.9937	pathogenic	-0.312	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.9043	likely_pathogenic	0.9	pathogenic	-1.37	Destabilizing	0.975	D	0.613	neutral	N	0.49514826	None	None	N
E/H	0.9814	likely_pathogenic	0.9815	pathogenic	-0.48	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
E/I	0.9599	likely_pathogenic	0.9582	pathogenic	0.023	Stabilizing	0.99	D	0.806	deleterious	None	None	None	None	N
E/K	0.93	likely_pathogenic	0.9306	pathogenic	-0.57	Destabilizing	0.065	N	0.331	neutral	N	0.471128522	None	None	N
E/L	0.9336	likely_pathogenic	0.9346	pathogenic	0.023	Stabilizing	0.98	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.9503	likely_pathogenic	0.9512	pathogenic	0.48	Stabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	N
E/N	0.9313	likely_pathogenic	0.9383	pathogenic	-1.133	Destabilizing	0.918	D	0.559	neutral	None	None	None	None	N
E/P	0.9724	likely_pathogenic	0.9756	pathogenic	-0.297	Destabilizing	0.935	D	0.717	prob.delet.	None	None	None	None	N
E/Q	0.8174	likely_pathogenic	0.8147	pathogenic	-1.001	Destabilizing	0.965	D	0.53	neutral	N	0.489561945	None	None	N
E/R	0.964	likely_pathogenic	0.9621	pathogenic	-0.225	Destabilizing	0.981	D	0.549	neutral	None	None	None	None	N
E/S	0.913	likely_pathogenic	0.9164	pathogenic	-1.452	Destabilizing	0.888	D	0.425	neutral	None	None	None	None	N
E/T	0.9511	likely_pathogenic	0.9496	pathogenic	-1.137	Destabilizing	0.987	D	0.614	neutral	None	None	None	None	N
E/V	0.8996	likely_pathogenic	0.8971	pathogenic	-0.297	Destabilizing	0.963	D	0.701	prob.neutral	N	0.508808743	None	None	N
E/W	0.9981	likely_pathogenic	0.9979	pathogenic	0.025	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/Y	0.9882	likely_pathogenic	0.9881	pathogenic	-0.03	Destabilizing	0.999	D	0.759	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.