TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31555	94888;94889;94890	chr2:178546765;178546764;178546763	chr2:179411492;179411491;179411490
N2AB	29914	89965;89966;89967	chr2:178546765;178546764;178546763	chr2:179411492;179411491;179411490
N2A	28987	87184;87185;87186	chr2:178546765;178546764;178546763	chr2:179411492;179411491;179411490
N2B	22490	67693;67694;67695	chr2:178546765;178546764;178546763	chr2:179411492;179411491;179411490
Novex-1	22615	68068;68069;68070	chr2:178546765;178546764;178546763	chr2:179411492;179411491;179411490
Novex-2	22682	68269;68270;68271	chr2:178546765;178546764;178546763	chr2:179411492;179411491;179411490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-118
• Domain position: 50
• Structural Position: 64
• Q(SASA): 0.4514
• 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
R/C	rs757099797	-0.48	1.0	N	0.811	0.421	0.785964137318	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.93E-06	0
R/C	rs757099797	-0.48	1.0	N	0.811	0.421	0.785964137318	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
R/C	rs757099797	-0.48	1.0	N	0.811	0.421	0.785964137318	gnomAD-4.0.0	7.43707E-06	None	None	None	None	N	None	4.00716E-05	3.33467E-05	None	0	0	None	0	0	5.93353E-06	0	0
R/G	rs757099797	-0.673	1.0	D	0.692	0.401	0.706445215409	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
R/G	rs757099797	-0.673	1.0	D	0.692	0.401	0.706445215409	gnomAD-4.0.0	4.78956E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11632E-05	0
R/H	rs727503545	-0.901	1.0	N	0.839	0.427	0.423597194605	gnomAD-2.1.1	6.8E-05	None	None	None	None	N	None	0	3.67938E-04	None	0	0	None	0	None	0	2.35E-05	4.21467E-04
R/H	rs727503545	-0.901	1.0	N	0.839	0.427	0.423597194605	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	0	2.62055E-04	0	0	0	None	0	0	1.47E-05	2.07211E-04	0
R/H	rs727503545	-0.901	1.0	N	0.839	0.427	0.423597194605	gnomAD-4.0.0	2.293E-05	None	None	None	None	N	None	0	4.16792E-04	None	3.37838E-05	0	None	0	0	5.93345E-06	1.09794E-05	4.80323E-05
R/L	rs727503545	None	1.0	D	0.692	0.388	0.705509371873	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79899E-06	0	0
R/S	None	None	1.0	N	0.721	0.419	0.542187413537	gnomAD-4.0.0	6.84226E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15955E-05	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
R/A	0.9	likely_pathogenic	0.8218	pathogenic	0.066	Stabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
R/C	0.5976	likely_pathogenic	0.4598	ambiguous	-0.332	Destabilizing	1.0	D	0.811	deleterious	N	0.515762455	None	None	N
R/D	0.949	likely_pathogenic	0.915	pathogenic	-0.307	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
R/E	0.8242	likely_pathogenic	0.7472	pathogenic	-0.253	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
R/F	0.9225	likely_pathogenic	0.8652	pathogenic	-0.258	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
R/G	0.7979	likely_pathogenic	0.6884	pathogenic	-0.083	Destabilizing	1.0	D	0.692	prob.neutral	D	0.524746705	None	None	N
R/H	0.2993	likely_benign	0.2279	benign	-0.611	Destabilizing	1.0	D	0.839	deleterious	N	0.490403271	None	None	N
R/I	0.7809	likely_pathogenic	0.6415	pathogenic	0.413	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
R/K	0.2321	likely_benign	0.1706	benign	-0.176	Destabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	N
R/L	0.7066	likely_pathogenic	0.5925	pathogenic	0.413	Stabilizing	1.0	D	0.692	prob.neutral	D	0.532115395	None	None	N
R/M	0.826	likely_pathogenic	0.709	pathogenic	-0.119	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
R/N	0.9215	likely_pathogenic	0.8681	pathogenic	-0.191	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
R/P	0.9078	likely_pathogenic	0.8332	pathogenic	0.316	Stabilizing	1.0	D	0.769	deleterious	N	0.49740471	None	None	N
R/Q	0.3033	likely_benign	0.2348	benign	-0.182	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
R/S	0.9193	likely_pathogenic	0.8614	pathogenic	-0.348	Destabilizing	1.0	D	0.721	prob.delet.	N	0.50527551	None	None	N
R/T	0.8289	likely_pathogenic	0.706	pathogenic	-0.18	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/V	0.8389	likely_pathogenic	0.729	pathogenic	0.316	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
R/W	0.5958	likely_pathogenic	0.4805	ambiguous	-0.461	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
R/Y	0.8164	likely_pathogenic	0.7144	pathogenic	-0.039	Destabilizing	1.0	D	0.784	deleterious	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.