TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34188	102787;102788;102789	chr2:178534053;178534052;178534051	chr2:179398780;179398779;179398778
N2AB	32547	97864;97865;97866	chr2:178534053;178534052;178534051	chr2:179398780;179398779;179398778
N2A	31620	95083;95084;95085	chr2:178534053;178534052;178534051	chr2:179398780;179398779;179398778
N2B	25123	75592;75593;75594	chr2:178534053;178534052;178534051	chr2:179398780;179398779;179398778
Novex-1	25248	75967;75968;75969	chr2:178534053;178534052;178534051	chr2:179398780;179398779;179398778
Novex-2	25315	76168;76169;76170	chr2:178534053;178534052;178534051	chr2:179398780;179398779;179398778
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-160
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4088
• 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	rs577667352	0.645	0.064	N	0.239	0.167	0.247322355667	gnomAD-2.1.1	5.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63399E-04	None	0	7.09E-05	0
E/K	rs577667352	0.645	0.064	N	0.239	0.167	0.247322355667	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	4.1425E-04	0
E/K	rs577667352	0.645	0.064	N	0.239	0.167	0.247322355667	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs577667352	0.645	0.064	N	0.239	0.167	0.247322355667	gnomAD-4.0.0	3.03603E-05	None	None	None	None	N	None	0	1.66628E-05	None	0	2.22806E-05	None	1.5624E-05	0	2.28842E-05	1.86649E-04	3.20061E-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	0.2022	likely_benign	0.1994	benign	-0.436	Destabilizing	None	N	0.174	neutral	N	0.496234739	None	None	N
E/C	0.853	likely_pathogenic	0.875	pathogenic	-0.309	Destabilizing	0.676	D	0.205	neutral	None	None	None	None	N
E/D	0.2116	likely_benign	0.2166	benign	-0.347	Destabilizing	None	N	0.187	neutral	N	0.474896675	None	None	N
E/F	0.8379	likely_pathogenic	0.8436	pathogenic	-0.118	Destabilizing	0.356	N	0.253	neutral	None	None	None	None	N
E/G	0.2547	likely_benign	0.2576	benign	-0.644	Destabilizing	0.012	N	0.243	neutral	N	0.485798596	None	None	N
E/H	0.3956	ambiguous	0.3883	ambiguous	0.277	Stabilizing	0.001	N	0.173	neutral	None	None	None	None	N
E/I	0.411	ambiguous	0.4238	ambiguous	0.086	Stabilizing	0.214	N	0.299	neutral	None	None	None	None	N
E/K	0.106	likely_benign	0.1032	benign	0.216	Stabilizing	0.064	N	0.239	neutral	N	0.513529634	None	None	N
E/L	0.4928	ambiguous	0.503	ambiguous	0.086	Stabilizing	0.038	N	0.339	neutral	None	None	None	None	N
E/M	0.5079	ambiguous	0.5181	ambiguous	0.034	Stabilizing	0.356	N	0.225	neutral	None	None	None	None	N
E/N	0.2847	likely_benign	0.2887	benign	-0.266	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
E/P	0.9328	likely_pathogenic	0.9395	pathogenic	-0.068	Destabilizing	0.072	N	0.304	neutral	None	None	None	None	N
E/Q	0.1076	likely_benign	0.106	benign	-0.196	Destabilizing	None	N	0.191	neutral	N	0.496234739	None	None	N
E/R	0.1841	likely_benign	0.1792	benign	0.548	Stabilizing	0.038	N	0.202	neutral	None	None	None	None	N
E/S	0.2256	likely_benign	0.2276	benign	-0.412	Destabilizing	0.001	N	0.133	neutral	None	None	None	None	N
E/T	0.2254	likely_benign	0.2287	benign	-0.23	Destabilizing	0.016	N	0.271	neutral	None	None	None	None	N
E/V	0.2592	likely_benign	0.2688	benign	-0.068	Destabilizing	0.029	N	0.335	neutral	N	0.511492193	None	None	N
E/W	0.9234	likely_pathogenic	0.9261	pathogenic	0.093	Stabilizing	0.864	D	0.215	neutral	None	None	None	None	N
E/Y	0.7051	likely_pathogenic	0.7088	pathogenic	0.134	Stabilizing	0.214	N	0.285	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.