TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16004	48235;48236;48237	chr2:178616879;178616878;178616877	chr2:179481606;179481605;179481604
N2AB	14363	43312;43313;43314	chr2:178616879;178616878;178616877	chr2:179481606;179481605;179481604
N2A	13436	40531;40532;40533	chr2:178616879;178616878;178616877	chr2:179481606;179481605;179481604
N2B	6939	21040;21041;21042	chr2:178616879;178616878;178616877	chr2:179481606;179481605;179481604
Novex-1	7064	21415;21416;21417	chr2:178616879;178616878;178616877	chr2:179481606;179481605;179481604
Novex-2	7131	21616;21617;21618	chr2:178616879;178616878;178616877	chr2:179481606;179481605;179481604
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-109
• Domain position: 37
• Structural Position: 69
• Q(SASA): 0.726
• 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	rs1305953554	0.409	0.712	N	0.352	0.084	0.286465849087	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
E/Q	rs1305953554	0.409	0.712	N	0.352	0.084	0.286465849087	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
E/Q	rs1305953554	0.409	0.712	N	0.352	0.084	0.286465849087	gnomAD-4.0.0	1.31673E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94525E-05	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	0.124	likely_benign	0.1309	benign	-0.021	Destabilizing	0.002	N	0.165	neutral	N	0.50574142	None	None	N
E/C	0.6904	likely_pathogenic	0.7161	pathogenic	-0.296	Destabilizing	0.977	D	0.329	neutral	None	None	None	None	N
E/D	0.123	likely_benign	0.1272	benign	-0.36	Destabilizing	0.201	N	0.343	neutral	N	0.511704312	None	None	N
E/F	0.6632	likely_pathogenic	0.6705	pathogenic	0.024	Stabilizing	0.92	D	0.339	neutral	None	None	None	None	N
E/G	0.1139	likely_benign	0.1151	benign	-0.157	Destabilizing	0.201	N	0.34	neutral	D	0.540020377	None	None	N
E/H	0.3054	likely_benign	0.327	benign	0.655	Stabilizing	0.92	D	0.366	neutral	None	None	None	None	N
E/I	0.3278	likely_benign	0.3493	ambiguous	0.285	Stabilizing	0.85	D	0.326	neutral	None	None	None	None	N
E/K	0.1081	likely_benign	0.1138	benign	0.383	Stabilizing	0.549	D	0.32	neutral	N	0.492368927	None	None	N
E/L	0.3021	likely_benign	0.3141	benign	0.285	Stabilizing	0.447	N	0.363	neutral	None	None	None	None	N
E/M	0.3744	ambiguous	0.387	ambiguous	-0.018	Destabilizing	0.977	D	0.325	neutral	None	None	None	None	N
E/N	0.1944	likely_benign	0.2017	benign	0.034	Stabilizing	0.021	N	0.206	neutral	None	None	None	None	N
E/P	0.2794	likely_benign	0.3081	benign	0.202	Stabilizing	0.92	D	0.359	neutral	None	None	None	None	N
E/Q	0.1057	likely_benign	0.1118	benign	0.066	Stabilizing	0.712	D	0.352	neutral	N	0.508366775	None	None	N
E/R	0.1855	likely_benign	0.1938	benign	0.68	Stabilizing	0.617	D	0.336	neutral	None	None	None	None	N
E/S	0.1498	likely_benign	0.1571	benign	-0.085	Destabilizing	0.25	N	0.345	neutral	None	None	None	None	N
E/T	0.1509	likely_benign	0.1611	benign	0.037	Stabilizing	0.002	N	0.161	neutral	None	None	None	None	N
E/V	0.1681	likely_benign	0.1809	benign	0.202	Stabilizing	0.379	N	0.353	neutral	N	0.510022535	None	None	N
E/W	0.8183	likely_pathogenic	0.8267	pathogenic	0.092	Stabilizing	0.992	D	0.398	neutral	None	None	None	None	N
E/Y	0.508	ambiguous	0.5308	ambiguous	0.252	Stabilizing	0.972	D	0.339	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.