TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27143	81652;81653;81654	chr2:178564705;178564704;178564703	chr2:179429432;179429431;179429430
N2AB	25502	76729;76730;76731	chr2:178564705;178564704;178564703	chr2:179429432;179429431;179429430
N2A	24575	73948;73949;73950	chr2:178564705;178564704;178564703	chr2:179429432;179429431;179429430
N2B	18078	54457;54458;54459	chr2:178564705;178564704;178564703	chr2:179429432;179429431;179429430
Novex-1	18203	54832;54833;54834	chr2:178564705;178564704;178564703	chr2:179429432;179429431;179429430
Novex-2	18270	55033;55034;55035	chr2:178564705;178564704;178564703	chr2:179429432;179429431;179429430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-85
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1005
• 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/C	rs1288732444	None	1.0	D	0.863	0.866	0.895945362441	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78011E-04
Y/C	rs1288732444	None	1.0	D	0.863	0.866	0.895945362441	gnomAD-4.0.0	6.5716E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78011E-04

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	0.9866	likely_pathogenic	0.9875	pathogenic	-3.535	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/C	0.8104	likely_pathogenic	0.814	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.679900834	None	None	N
Y/D	0.9918	likely_pathogenic	0.9912	pathogenic	-3.867	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.679900834	None	None	N
Y/E	0.9957	likely_pathogenic	0.996	pathogenic	-3.686	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/F	0.2817	likely_benign	0.2896	benign	-1.414	Destabilizing	0.999	D	0.755	deleterious	D	0.627008372	None	None	N
Y/G	0.978	likely_pathogenic	0.9793	pathogenic	-3.908	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/H	0.9094	likely_pathogenic	0.9227	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.663881473	None	None	N
Y/I	0.9011	likely_pathogenic	0.9139	pathogenic	-2.273	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/K	0.988	likely_pathogenic	0.9903	pathogenic	-2.556	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/L	0.9065	likely_pathogenic	0.9126	pathogenic	-2.273	Highly Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
Y/M	0.9502	likely_pathogenic	0.9535	pathogenic	-1.907	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/N	0.9105	likely_pathogenic	0.9171	pathogenic	-3.268	Highly Destabilizing	1.0	D	0.856	deleterious	D	0.67969903	None	None	N
Y/P	0.9991	likely_pathogenic	0.9991	pathogenic	-2.711	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9904	likely_pathogenic	0.9917	pathogenic	-3.086	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/R	0.9715	likely_pathogenic	0.9765	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/S	0.9679	likely_pathogenic	0.9698	pathogenic	-3.581	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.679900834	None	None	N
Y/T	0.9783	likely_pathogenic	0.98	pathogenic	-3.3	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/V	0.8253	likely_pathogenic	0.8448	pathogenic	-2.711	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/W	0.7749	likely_pathogenic	0.7851	pathogenic	-0.772	Destabilizing	1.0	D	0.822	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.