TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25980	78163;78164;78165	chr2:178568194;178568193;178568192	chr2:179432921;179432920;179432919
N2AB	24339	73240;73241;73242	chr2:178568194;178568193;178568192	chr2:179432921;179432920;179432919
N2A	23412	70459;70460;70461	chr2:178568194;178568193;178568192	chr2:179432921;179432920;179432919
N2B	16915	50968;50969;50970	chr2:178568194;178568193;178568192	chr2:179432921;179432920;179432919
Novex-1	17040	51343;51344;51345	chr2:178568194;178568193;178568192	chr2:179432921;179432920;179432919
Novex-2	17107	51544;51545;51546	chr2:178568194;178568193;178568192	chr2:179432921;179432920;179432919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-76
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.8211
• 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
D/E	rs977275961	0.093	None	N	0.081	0.086	0.0401082797425	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
D/E	rs977275961	0.093	None	N	0.081	0.086	0.0401082797425	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs977275961	0.093	None	N	0.081	0.086	0.0401082797425	gnomAD-4.0.0	1.31574E-05	None	None	None	None	N	None	4.82882E-05	0	None	0	0	None	0	0	0	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
D/A	0.0666	likely_benign	0.0682	benign	-0.252	Destabilizing	None	N	0.355	neutral	N	0.482651288	None	None	N
D/C	0.2849	likely_benign	0.2791	benign	-0.239	Destabilizing	0.747	D	0.449	neutral	None	None	None	None	N
D/E	0.0665	likely_benign	0.0613	benign	-0.314	Destabilizing	None	N	0.081	neutral	N	0.387700899	None	None	N
D/F	0.2906	likely_benign	0.3164	benign	0.137	Stabilizing	0.204	N	0.492	neutral	None	None	None	None	N
D/G	0.1004	likely_benign	0.1016	benign	-0.501	Destabilizing	0.006	N	0.391	neutral	N	0.46374024	None	None	N
D/H	0.1291	likely_benign	0.1365	benign	0.403	Stabilizing	0.087	N	0.446	neutral	N	0.48914019	None	None	N
D/I	0.1145	likely_benign	0.1193	benign	0.373	Stabilizing	0.112	N	0.569	neutral	None	None	None	None	N
D/K	0.1015	likely_benign	0.1064	benign	0.18	Stabilizing	0.007	N	0.425	neutral	None	None	None	None	N
D/L	0.1206	likely_benign	0.1269	benign	0.373	Stabilizing	0.035	N	0.533	neutral	None	None	None	None	N
D/M	0.2099	likely_benign	0.2104	benign	0.336	Stabilizing	0.492	N	0.447	neutral	None	None	None	None	N
D/N	0.0659	likely_benign	0.0663	benign	-0.329	Destabilizing	None	N	0.209	neutral	N	0.496794021	None	None	N
D/P	0.1785	likely_benign	0.1886	benign	0.188	Stabilizing	0.068	N	0.559	neutral	None	None	None	None	N
D/Q	0.1049	likely_benign	0.1037	benign	-0.23	Destabilizing	None	N	0.209	neutral	None	None	None	None	N
D/R	0.1509	likely_benign	0.1627	benign	0.51	Stabilizing	0.018	N	0.513	neutral	None	None	None	None	N
D/S	0.0661	likely_benign	0.0655	benign	-0.45	Destabilizing	None	N	0.124	neutral	None	None	None	None	N
D/T	0.0872	likely_benign	0.0872	benign	-0.237	Destabilizing	0.018	N	0.453	neutral	None	None	None	None	N
D/V	0.0767	likely_benign	0.081	benign	0.188	Stabilizing	0.013	N	0.561	neutral	N	0.49463915	None	None	N
D/W	0.6873	likely_pathogenic	0.7295	pathogenic	0.341	Stabilizing	0.747	D	0.534	neutral	None	None	None	None	N
D/Y	0.1349	likely_benign	0.1482	benign	0.399	Stabilizing	0.162	N	0.515	neutral	N	0.471289425	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.