TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29877	89854;89855;89856	chr2:178553271;178553270;178553269	chr2:179417998;179417997;179417996
N2AB	28236	84931;84932;84933	chr2:178553271;178553270;178553269	chr2:179417998;179417997;179417996
N2A	27309	82150;82151;82152	chr2:178553271;178553270;178553269	chr2:179417998;179417997;179417996
N2B	20812	62659;62660;62661	chr2:178553271;178553270;178553269	chr2:179417998;179417997;179417996
Novex-1	20937	63034;63035;63036	chr2:178553271;178553270;178553269	chr2:179417998;179417997;179417996
Novex-2	21004	63235;63236;63237	chr2:178553271;178553270;178553269	chr2:179417998;179417997;179417996
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: Ig-147
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.6619
• 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/D	rs767080000	-0.028	0.004	N	0.181	0.083	0.166414681773	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.41849E-04	None	0	None	0	0	0
E/D	rs767080000	-0.028	0.004	N	0.181	0.083	0.166414681773	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92604E-04	None	0	0	0	0	0
E/D	rs767080000	-0.028	0.004	N	0.181	0.083	0.166414681773	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	0	0	None	0	1.92604E-04	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
E/A	0.1791	likely_benign	0.1816	benign	-0.085	Destabilizing	0.896	D	0.394	neutral	N	0.489051611	None	None	N
E/C	0.801	likely_pathogenic	0.8103	pathogenic	-0.091	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
E/D	0.0844	likely_benign	0.0844	benign	-0.187	Destabilizing	0.004	N	0.181	neutral	N	0.384345589	None	None	N
E/F	0.7523	likely_pathogenic	0.7432	pathogenic	-0.06	Destabilizing	0.996	D	0.555	neutral	None	None	None	None	N
E/G	0.0898	likely_benign	0.0937	benign	-0.235	Destabilizing	0.896	D	0.413	neutral	N	0.347704424	None	None	N
E/H	0.401	ambiguous	0.4225	ambiguous	0.416	Stabilizing	0.996	D	0.367	neutral	None	None	None	None	N
E/I	0.4067	ambiguous	0.4016	ambiguous	0.259	Stabilizing	0.988	D	0.543	neutral	None	None	None	None	N
E/K	0.1356	likely_benign	0.1423	benign	0.426	Stabilizing	0.896	D	0.427	neutral	N	0.465558676	None	None	N
E/L	0.4402	ambiguous	0.4382	ambiguous	0.259	Stabilizing	0.988	D	0.541	neutral	None	None	None	None	N
E/M	0.4615	ambiguous	0.4526	ambiguous	0.111	Stabilizing	0.999	D	0.489	neutral	None	None	None	None	N
E/N	0.1613	likely_benign	0.1748	benign	0.194	Stabilizing	0.851	D	0.367	neutral	None	None	None	None	N
E/P	0.6027	likely_pathogenic	0.6138	pathogenic	0.164	Stabilizing	0.988	D	0.398	neutral	None	None	None	None	N
E/Q	0.1375	likely_benign	0.1436	benign	0.217	Stabilizing	0.946	D	0.399	neutral	N	0.502154194	None	None	N
E/R	0.2387	likely_benign	0.2527	benign	0.659	Stabilizing	0.988	D	0.382	neutral	None	None	None	None	N
E/S	0.1622	likely_benign	0.1676	benign	0.026	Stabilizing	0.919	D	0.396	neutral	None	None	None	None	N
E/T	0.2065	likely_benign	0.213	benign	0.152	Stabilizing	0.959	D	0.385	neutral	None	None	None	None	N
E/V	0.2748	likely_benign	0.2698	benign	0.164	Stabilizing	0.984	D	0.431	neutral	N	0.467657531	None	None	N
E/W	0.8618	likely_pathogenic	0.8518	pathogenic	0.018	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	N
E/Y	0.588	likely_pathogenic	0.5816	pathogenic	0.172	Stabilizing	0.996	D	0.481	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.