TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27256	81991;81992;81993	chr2:178564366;178564365;178564364	chr2:179429093;179429092;179429091
N2AB	25615	77068;77069;77070	chr2:178564366;178564365;178564364	chr2:179429093;179429092;179429091
N2A	24688	74287;74288;74289	chr2:178564366;178564365;178564364	chr2:179429093;179429092;179429091
N2B	18191	54796;54797;54798	chr2:178564366;178564365;178564364	chr2:179429093;179429092;179429091
Novex-1	18316	55171;55172;55173	chr2:178564366;178564365;178564364	chr2:179429093;179429092;179429091
Novex-2	18383	55372;55373;55374	chr2:178564366;178564365;178564364	chr2:179429093;179429092;179429091
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: Fn3-86
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6718
• 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/G	rs748963818	-0.812	0.521	N	0.554	0.207	0.376393476264	gnomAD-2.1.1	4.43E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.59477E-04	None	0	0	0
E/G	rs748963818	-0.812	0.521	N	0.554	0.207	0.376393476264	gnomAD-4.0.0	1.09481E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99484E-07	1.73897E-04	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	0.104	likely_benign	0.0989	benign	-0.41	Destabilizing	0.472	N	0.517	neutral	N	0.496874166	None	None	N
E/C	0.7203	likely_pathogenic	0.7131	pathogenic	-0.17	Destabilizing	0.996	D	0.564	neutral	None	None	None	None	N
E/D	0.1124	likely_benign	0.1095	benign	-0.35	Destabilizing	0.309	N	0.498	neutral	N	0.449621723	None	None	N
E/F	0.5757	likely_pathogenic	0.5606	ambiguous	-0.158	Destabilizing	0.953	D	0.577	neutral	None	None	None	None	N
E/G	0.1439	likely_benign	0.1397	benign	-0.621	Destabilizing	0.521	D	0.554	neutral	N	0.480243101	None	None	N
E/H	0.3793	ambiguous	0.3691	ambiguous	0.152	Stabilizing	0.02	N	0.237	neutral	None	None	None	None	N
E/I	0.1917	likely_benign	0.1972	benign	0.115	Stabilizing	0.59	D	0.644	neutral	None	None	None	None	N
E/K	0.0906	likely_benign	0.089	benign	0.259	Stabilizing	0.309	N	0.499	neutral	N	0.487619964	None	None	N
E/L	0.198	likely_benign	0.1932	benign	0.115	Stabilizing	0.59	D	0.562	neutral	None	None	None	None	N
E/M	0.2789	likely_benign	0.276	benign	0.152	Stabilizing	0.953	D	0.565	neutral	None	None	None	None	N
E/N	0.1877	likely_benign	0.1848	benign	-0.156	Destabilizing	0.009	N	0.181	neutral	None	None	None	None	N
E/P	0.2818	likely_benign	0.2718	benign	-0.04	Destabilizing	0.984	D	0.645	neutral	None	None	None	None	N
E/Q	0.1077	likely_benign	0.1075	benign	-0.095	Destabilizing	0.684	D	0.565	neutral	N	0.521020462	None	None	N
E/R	0.1851	likely_benign	0.1846	benign	0.539	Stabilizing	0.004	N	0.129	neutral	None	None	None	None	N
E/S	0.149	likely_benign	0.1481	benign	-0.314	Destabilizing	0.59	D	0.481	neutral	None	None	None	None	N
E/T	0.1731	likely_benign	0.171	benign	-0.135	Destabilizing	0.742	D	0.581	neutral	None	None	None	None	N
E/V	0.1224	likely_benign	0.1251	benign	-0.04	Destabilizing	0.028	N	0.4	neutral	N	0.505725722	None	None	N
E/W	0.8587	likely_pathogenic	0.847	pathogenic	0.033	Stabilizing	0.996	D	0.61	neutral	None	None	None	None	N
E/Y	0.4502	ambiguous	0.4427	ambiguous	0.093	Stabilizing	0.91	D	0.595	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.