TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25743	77452;77453;77454	chr2:178568905;178568904;178568903	chr2:179433632;179433631;179433630
N2AB	24102	72529;72530;72531	chr2:178568905;178568904;178568903	chr2:179433632;179433631;179433630
N2A	23175	69748;69749;69750	chr2:178568905;178568904;178568903	chr2:179433632;179433631;179433630
N2B	16678	50257;50258;50259	chr2:178568905;178568904;178568903	chr2:179433632;179433631;179433630
Novex-1	16803	50632;50633;50634	chr2:178568905;178568904;178568903	chr2:179433632;179433631;179433630
Novex-2	16870	50833;50834;50835	chr2:178568905;178568904;178568903	chr2:179433632;179433631;179433630
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: Fn3-75
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9039
• 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	rs765997807	0.665	0.22	N	0.56	0.214	0.273070737957	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/K	rs765997807	0.665	0.22	N	0.56	0.214	0.273070737957	gnomAD-4.0.0	2.73771E-06	None	None	None	None	N	None	0	0	None	0	2.5208E-05	None	0	0	1.79923E-06	0	1.65695E-05
E/Q	None	None	0.22	N	0.541	0.152	0.265929055128	gnomAD-4.0.0	6.84428E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99614E-07	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	0.1892	likely_benign	0.175	benign	0.005	Stabilizing	0.22	N	0.572	neutral	N	0.50786195	None	None	N
E/C	0.8505	likely_pathogenic	0.8475	pathogenic	-0.219	Destabilizing	0.968	D	0.667	neutral	None	None	None	None	N
E/D	0.0777	likely_benign	0.0751	benign	-0.39	Destabilizing	None	N	0.252	neutral	N	0.417338733	None	None	N
E/F	0.8109	likely_pathogenic	0.8003	pathogenic	-0.089	Destabilizing	0.89	D	0.618	neutral	None	None	None	None	N
E/G	0.1243	likely_benign	0.1228	benign	-0.081	Destabilizing	0.22	N	0.536	neutral	N	0.454814112	None	None	N
E/H	0.5013	ambiguous	0.4644	ambiguous	0.534	Stabilizing	0.726	D	0.613	neutral	None	None	None	None	N
E/I	0.4513	ambiguous	0.4353	ambiguous	0.172	Stabilizing	0.726	D	0.618	neutral	None	None	None	None	N
E/K	0.1786	likely_benign	0.1717	benign	0.365	Stabilizing	0.22	N	0.56	neutral	N	0.488929473	None	None	N
E/L	0.4262	ambiguous	0.416	ambiguous	0.172	Stabilizing	0.567	D	0.604	neutral	None	None	None	None	N
E/M	0.5208	ambiguous	0.5145	ambiguous	-0.043	Destabilizing	0.968	D	0.623	neutral	None	None	None	None	N
E/N	0.1953	likely_benign	0.1813	benign	0.168	Stabilizing	0.157	N	0.576	neutral	None	None	None	None	N
E/P	0.402	ambiguous	0.3819	ambiguous	0.133	Stabilizing	0.726	D	0.591	neutral	None	None	None	None	N
E/Q	0.1683	likely_benign	0.1561	benign	0.164	Stabilizing	0.22	N	0.541	neutral	N	0.488409398	None	None	N
E/R	0.3186	likely_benign	0.3072	benign	0.558	Stabilizing	0.567	D	0.597	neutral	None	None	None	None	N
E/S	0.1753	likely_benign	0.1647	benign	0.035	Stabilizing	0.157	N	0.565	neutral	None	None	None	None	N
E/T	0.2302	likely_benign	0.2148	benign	0.116	Stabilizing	0.272	N	0.543	neutral	None	None	None	None	N
E/V	0.2768	likely_benign	0.2672	benign	0.133	Stabilizing	0.667	D	0.561	neutral	N	0.514499921	None	None	N
E/W	0.8973	likely_pathogenic	0.8967	pathogenic	-0.072	Destabilizing	0.968	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.678	likely_pathogenic	0.6657	pathogenic	0.122	Stabilizing	0.89	D	0.613	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.