TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14475	43648;43649;43650	chr2:178632583;178632582;178632581	chr2:179497310;179497309;179497308
N2AB	12834	38725;38726;38727	chr2:178632583;178632582;178632581	chr2:179497310;179497309;179497308
N2A	11907	35944;35945;35946	chr2:178632583;178632582;178632581	chr2:179497310;179497309;179497308
N2B	5410	16453;16454;16455	chr2:178632583;178632582;178632581	chr2:179497310;179497309;179497308
Novex-1	5535	16828;16829;16830	chr2:178632583;178632582;178632581	chr2:179497310;179497309;179497308
Novex-2	5602	17029;17030;17031	chr2:178632583;178632582;178632581	chr2:179497310;179497309;179497308
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-95
• Domain position: 68
• Structural Position: 152
• Q(SASA): 0.1615
• 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
A/G	None	None	0.002	N	0.473	0.067	0.0482279557977	gnomAD-4.0.0	9.58168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.2595E-05	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
A/C	0.7892	likely_pathogenic	0.715	pathogenic	-0.719	Destabilizing	0.982	D	0.758	deleterious	None	None	None	None	N
A/D	0.5243	ambiguous	0.454	ambiguous	-1.311	Destabilizing	0.7	D	0.765	deleterious	None	None	None	None	N
A/E	0.5912	likely_pathogenic	0.5266	ambiguous	-1.252	Destabilizing	0.781	D	0.772	deleterious	D	0.615642753	None	None	N
A/F	0.8103	likely_pathogenic	0.7703	pathogenic	-0.796	Destabilizing	0.7	D	0.774	deleterious	None	None	None	None	N
A/G	0.0863	likely_benign	0.0645	benign	-1.208	Destabilizing	0.002	N	0.473	neutral	N	0.396679114	None	None	N
A/H	0.8887	likely_pathogenic	0.8578	pathogenic	-1.461	Destabilizing	0.982	D	0.769	deleterious	None	None	None	None	N
A/I	0.8486	likely_pathogenic	0.8129	pathogenic	-0.026	Destabilizing	0.539	D	0.78	deleterious	None	None	None	None	N
A/K	0.8628	likely_pathogenic	0.8095	pathogenic	-1.169	Destabilizing	0.7	D	0.774	deleterious	None	None	None	None	N
A/L	0.6592	likely_pathogenic	0.5948	pathogenic	-0.026	Destabilizing	0.25	N	0.725	prob.delet.	None	None	None	None	N
A/M	0.6643	likely_pathogenic	0.6202	pathogenic	0.003	Stabilizing	0.947	D	0.763	deleterious	None	None	None	None	N
A/N	0.5732	likely_pathogenic	0.514	ambiguous	-1.079	Destabilizing	0.7	D	0.773	deleterious	None	None	None	None	N
A/P	0.9738	likely_pathogenic	0.9707	pathogenic	-0.26	Destabilizing	0.781	D	0.77	deleterious	D	0.618355604	None	None	N
A/Q	0.7087	likely_pathogenic	0.629	pathogenic	-1.092	Destabilizing	0.826	D	0.761	deleterious	None	None	None	None	N
A/R	0.7689	likely_pathogenic	0.6981	pathogenic	-0.97	Destabilizing	0.826	D	0.766	deleterious	None	None	None	None	N
A/S	0.1191	likely_benign	0.1175	benign	-1.473	Destabilizing	0.201	N	0.711	prob.delet.	N	0.505749689	None	None	N
A/T	0.2597	likely_benign	0.2321	benign	-1.303	Destabilizing	0.334	N	0.746	deleterious	D	0.576509501	None	None	N
A/V	0.5317	ambiguous	0.486	ambiguous	-0.26	Destabilizing	0.004	N	0.509	neutral	D	0.618230155	None	None	N
A/W	0.9683	likely_pathogenic	0.9502	pathogenic	-1.338	Destabilizing	0.982	D	0.739	prob.delet.	None	None	None	None	N
A/Y	0.8868	likely_pathogenic	0.8515	pathogenic	-0.824	Destabilizing	0.826	D	0.782	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.