TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16659	50200;50201;50202	chr2:178612550;178612549;178612548	chr2:179477277;179477276;179477275
N2AB	15018	45277;45278;45279	chr2:178612550;178612549;178612548	chr2:179477277;179477276;179477275
N2A	14091	42496;42497;42498	chr2:178612550;178612549;178612548	chr2:179477277;179477276;179477275
N2B	7594	23005;23006;23007	chr2:178612550;178612549;178612548	chr2:179477277;179477276;179477275
Novex-1	7719	23380;23381;23382	chr2:178612550;178612549;178612548	chr2:179477277;179477276;179477275
Novex-2	7786	23581;23582;23583	chr2:178612550;178612549;178612548	chr2:179477277;179477276;179477275
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: Fn3-9
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5767
• 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	rs778767799	0.158	0.98	N	0.551	0.301	0.250039746154	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.25E-06	0
E/K	rs778767799	0.158	0.98	N	0.551	0.301	0.250039746154	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.45E-05	0	0	0	0
E/K	rs778767799	0.158	0.98	N	0.551	0.301	0.250039746154	gnomAD-4.0.0	6.4271E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.58519E-05	0	9.59168E-06	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	0.5689	likely_pathogenic	0.6925	pathogenic	-0.52	Destabilizing	0.98	D	0.604	neutral	N	0.471622492	None	None	N
E/C	0.9788	likely_pathogenic	0.9883	pathogenic	-0.35	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/D	0.503	ambiguous	0.4497	ambiguous	-0.793	Destabilizing	0.031	N	0.19	neutral	N	0.480954813	None	None	N
E/F	0.9811	likely_pathogenic	0.9906	pathogenic	0.179	Stabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
E/G	0.7489	likely_pathogenic	0.8368	pathogenic	-0.869	Destabilizing	0.98	D	0.665	neutral	N	0.514536692	None	None	N
E/H	0.8702	likely_pathogenic	0.9342	pathogenic	0.155	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
E/I	0.8577	likely_pathogenic	0.9127	pathogenic	0.423	Stabilizing	0.983	D	0.772	deleterious	None	None	None	None	N
E/K	0.6271	likely_pathogenic	0.7992	pathogenic	-0.158	Destabilizing	0.98	D	0.551	neutral	N	0.435153728	None	None	N
E/L	0.8656	likely_pathogenic	0.9148	pathogenic	0.423	Stabilizing	0.191	N	0.471	neutral	None	None	None	None	N
E/M	0.8616	likely_pathogenic	0.9185	pathogenic	0.576	Stabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
E/N	0.7978	likely_pathogenic	0.8481	pathogenic	-0.835	Destabilizing	0.991	D	0.559	neutral	None	None	None	None	N
E/P	0.997	likely_pathogenic	0.9978	pathogenic	0.131	Stabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/Q	0.3895	ambiguous	0.5264	ambiguous	-0.677	Destabilizing	0.994	D	0.565	neutral	N	0.476988018	None	None	N
E/R	0.747	likely_pathogenic	0.8712	pathogenic	0.188	Stabilizing	0.996	D	0.595	neutral	None	None	None	None	N
E/S	0.6399	likely_pathogenic	0.7405	pathogenic	-1.051	Destabilizing	0.97	D	0.537	neutral	None	None	None	None	N
E/T	0.643	likely_pathogenic	0.7641	pathogenic	-0.752	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
E/V	0.65	likely_pathogenic	0.7628	pathogenic	0.131	Stabilizing	0.925	D	0.661	neutral	N	0.474410184	None	None	N
E/W	0.9921	likely_pathogenic	0.9967	pathogenic	0.454	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Y	0.9562	likely_pathogenic	0.9777	pathogenic	0.449	Stabilizing	0.999	D	0.786	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.