TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6807	20644;20645;20646	chr2:178725903;178725902;178725901	chr2:179590630;179590629;179590628
N2AB	6490	19693;19694;19695	chr2:178725903;178725902;178725901	chr2:179590630;179590629;179590628
N2A	5563	16912;16913;16914	chr2:178725903;178725902;178725901	chr2:179590630;179590629;179590628
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-52
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1517
• 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
Y/H	None	None	0.535	D	0.37	0.261	0.39694197178	gnomAD-4.0.0	1.36897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79943E-06	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
Y/A	0.9524	likely_pathogenic	0.9144	pathogenic	-2.943	Highly Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
Y/C	0.4688	ambiguous	0.3803	ambiguous	-1.992	Destabilizing	1.0	D	0.735	prob.delet.	N	0.520196681	None	None	N
Y/D	0.9652	likely_pathogenic	0.9428	pathogenic	-2.717	Highly Destabilizing	1.0	D	0.779	deleterious	D	0.538807915	None	None	N
Y/E	0.9802	likely_pathogenic	0.9664	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
Y/F	0.1328	likely_benign	0.1182	benign	-1.091	Destabilizing	0.997	D	0.541	neutral	N	0.495021231	None	None	N
Y/G	0.9383	likely_pathogenic	0.9044	pathogenic	-3.372	Highly Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
Y/H	0.6192	likely_pathogenic	0.5272	ambiguous	-1.912	Destabilizing	0.535	D	0.37	neutral	D	0.525594854	None	None	N
Y/I	0.7408	likely_pathogenic	0.6691	pathogenic	-1.549	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
Y/K	0.9762	likely_pathogenic	0.9631	pathogenic	-2.169	Highly Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
Y/L	0.7751	likely_pathogenic	0.6956	pathogenic	-1.549	Destabilizing	0.992	D	0.625	neutral	None	None	None	None	N
Y/M	0.8533	likely_pathogenic	0.8004	pathogenic	-1.387	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
Y/N	0.7484	likely_pathogenic	0.644	pathogenic	-2.874	Highly Destabilizing	1.0	D	0.708	prob.delet.	D	0.523412685	None	None	N
Y/P	0.9968	likely_pathogenic	0.9952	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
Y/Q	0.9413	likely_pathogenic	0.9009	pathogenic	-2.614	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
Y/R	0.9414	likely_pathogenic	0.9113	pathogenic	-1.91	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
Y/S	0.8743	likely_pathogenic	0.7913	pathogenic	-3.356	Highly Destabilizing	1.0	D	0.68	prob.neutral	N	0.519689702	None	None	N
Y/T	0.9167	likely_pathogenic	0.8659	pathogenic	-3.037	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
Y/V	0.6665	likely_pathogenic	0.6021	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
Y/W	0.646	likely_pathogenic	0.6042	pathogenic	-0.452	Destabilizing	1.0	D	0.645	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.