TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23227	69904;69905;69906	chr2:178576565;178576564;178576563	chr2:179441292;179441291;179441290
N2AB	21586	64981;64982;64983	chr2:178576565;178576564;178576563	chr2:179441292;179441291;179441290
N2A	20659	62200;62201;62202	chr2:178576565;178576564;178576563	chr2:179441292;179441291;179441290
N2B	14162	42709;42710;42711	chr2:178576565;178576564;178576563	chr2:179441292;179441291;179441290
Novex-1	14287	43084;43085;43086	chr2:178576565;178576564;178576563	chr2:179441292;179441291;179441290
Novex-2	14354	43285;43286;43287	chr2:178576565;178576564;178576563	chr2:179441292;179441291;179441290
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: Fn3-56
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.7377
• Predicted PPI site: I

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	rs765429292	0.793	0.03	N	0.417	0.088	0.259761712551	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs765429292	0.793	0.03	N	0.417	0.088	0.259761712551	gnomAD-4.0.0	1.3686E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99556E-07	1.15974E-05	0
E/Q	rs765429292	None	0.002	N	0.212	0.107	0.197625483188	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs765429292	None	0.002	N	0.212	0.107	0.197625483188	gnomAD-4.0.0	1.85934E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54313E-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	0.0891	likely_benign	0.0846	benign	-0.394	Destabilizing	None	N	0.215	neutral	N	0.498852891	None	None	I
E/C	0.6169	likely_pathogenic	0.5874	pathogenic	-0.07	Destabilizing	0.685	D	0.427	neutral	None	None	None	None	I
E/D	0.0822	likely_benign	0.0748	benign	-0.333	Destabilizing	None	N	0.166	neutral	N	0.451080374	None	None	I
E/F	0.5341	ambiguous	0.4884	ambiguous	-0.24	Destabilizing	0.366	N	0.433	neutral	None	None	None	None	I
E/G	0.1141	likely_benign	0.1098	benign	-0.583	Destabilizing	0.012	N	0.385	neutral	N	0.467379085	None	None	I
E/H	0.2954	likely_benign	0.2826	benign	0.062	Stabilizing	0.366	N	0.514	neutral	None	None	None	None	I
E/I	0.2048	likely_benign	0.1854	benign	0.071	Stabilizing	0.221	N	0.477	neutral	None	None	None	None	I
E/K	0.0944	likely_benign	0.0943	benign	0.363	Stabilizing	0.03	N	0.417	neutral	N	0.466319185	None	None	I
E/L	0.1989	likely_benign	0.1833	benign	0.071	Stabilizing	0.039	N	0.515	neutral	None	None	None	None	I
E/M	0.2794	likely_benign	0.2552	benign	0.15	Stabilizing	0.869	D	0.468	neutral	None	None	None	None	I
E/N	0.1545	likely_benign	0.1369	benign	-0.015	Destabilizing	0.039	N	0.473	neutral	None	None	None	None	I
E/P	0.204	likely_benign	0.1856	benign	-0.064	Destabilizing	None	N	0.301	neutral	None	None	None	None	I
E/Q	0.1108	likely_benign	0.11	benign	0.024	Stabilizing	0.002	N	0.212	neutral	N	0.505992294	None	None	I
E/R	0.161	likely_benign	0.1623	benign	0.581	Stabilizing	0.075	N	0.477	neutral	None	None	None	None	I
E/S	0.1246	likely_benign	0.1146	benign	-0.161	Destabilizing	0.016	N	0.407	neutral	None	None	None	None	I
E/T	0.1466	likely_benign	0.1357	benign	None	Stabilizing	0.075	N	0.527	neutral	None	None	None	None	I
E/V	0.1221	likely_benign	0.1133	benign	-0.064	Destabilizing	0.03	N	0.479	neutral	D	0.523231261	None	None	I
E/W	0.7466	likely_pathogenic	0.7242	pathogenic	-0.071	Destabilizing	0.869	D	0.484	neutral	None	None	None	None	I
E/Y	0.3986	ambiguous	0.3638	ambiguous	0.011	Stabilizing	0.637	D	0.489	neutral	None	None	None	None	I

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.