TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14502	43729;43730;43731	chr2:178632390;178632389;178632388	chr2:179497117;179497116;179497115
N2AB	12861	38806;38807;38808	chr2:178632390;178632389;178632388	chr2:179497117;179497116;179497115
N2A	11934	36025;36026;36027	chr2:178632390;178632389;178632388	chr2:179497117;179497116;179497115
N2B	5437	16534;16535;16536	chr2:178632390;178632389;178632388	chr2:179497117;179497116;179497115
Novex-1	5562	16909;16910;16911	chr2:178632390;178632389;178632388	chr2:179497117;179497116;179497115
Novex-2	5629	17110;17111;17112	chr2:178632390;178632389;178632388	chr2:179497117;179497116;179497115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-96
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4572
• 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
P/R	None	None	1.0	D	0.767	0.49	0.693704026606	gnomAD-4.0.0	6.93061E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06001E-07	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
P/A	0.1707	likely_benign	0.1452	benign	-0.957	Destabilizing	1.0	D	0.752	deleterious	D	0.558998015	None	None	N
P/C	0.8298	likely_pathogenic	0.7634	pathogenic	-0.704	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
P/D	0.7131	likely_pathogenic	0.6699	pathogenic	-0.415	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/E	0.5267	ambiguous	0.4933	ambiguous	-0.426	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/F	0.8269	likely_pathogenic	0.7642	pathogenic	-0.673	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
P/G	0.6119	likely_pathogenic	0.515	ambiguous	-1.239	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/H	0.4087	ambiguous	0.3594	ambiguous	-0.679	Destabilizing	1.0	D	0.721	prob.delet.	D	0.539645421	None	None	N
P/I	0.6756	likely_pathogenic	0.61	pathogenic	-0.306	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/K	0.5708	likely_pathogenic	0.5205	ambiguous	-0.736	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
P/L	0.289	likely_benign	0.251	benign	-0.306	Destabilizing	1.0	D	0.797	deleterious	D	0.643352249	None	None	N
P/M	0.6583	likely_pathogenic	0.591	pathogenic	-0.358	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
P/N	0.6515	likely_pathogenic	0.5863	pathogenic	-0.57	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
P/Q	0.3605	ambiguous	0.3231	benign	-0.697	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/R	0.3788	ambiguous	0.3361	benign	-0.29	Destabilizing	1.0	D	0.767	deleterious	D	0.602318152	None	None	N
P/S	0.265	likely_benign	0.2279	benign	-1.1	Destabilizing	1.0	D	0.817	deleterious	D	0.560152803	None	None	N
P/T	0.2767	likely_benign	0.239	benign	-0.993	Destabilizing	1.0	D	0.817	deleterious	D	0.559868037	None	None	N
P/V	0.5127	ambiguous	0.4466	ambiguous	-0.486	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/W	0.9212	likely_pathogenic	0.8795	pathogenic	-0.836	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
P/Y	0.7514	likely_pathogenic	0.6823	pathogenic	-0.52	Destabilizing	1.0	D	0.738	prob.delet.	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.