TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35167	105724;105725;105726	chr2:178531116;178531115;178531114	chr2:179395843;179395842;179395841
N2AB	33526	100801;100802;100803	chr2:178531116;178531115;178531114	chr2:179395843;179395842;179395841
N2A	32599	98020;98021;98022	chr2:178531116;178531115;178531114	chr2:179395843;179395842;179395841
N2B	26102	78529;78530;78531	chr2:178531116;178531115;178531114	chr2:179395843;179395842;179395841
Novex-1	26227	78904;78905;78906	chr2:178531116;178531115;178531114	chr2:179395843;179395842;179395841
Novex-2	26294	79105;79106;79107	chr2:178531116;178531115;178531114	chr2:179395843;179395842;179395841
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-164
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.4604
• 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
Q/E	rs1558994144	None	0.789	N	0.269	0.088	0.158396225186	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/E	rs1558994144	None	0.789	N	0.269	0.088	0.158396225186	gnomAD-4.0.0	2.73654E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79879E-06	1.15931E-05	1.65634E-05

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
Q/A	0.2087	likely_benign	0.1923	benign	-0.108	Destabilizing	0.832	D	0.343	neutral	None	None	None	None	N
Q/C	0.624	likely_pathogenic	0.567	pathogenic	-0.055	Destabilizing	0.999	D	0.331	neutral	None	None	None	None	N
Q/D	0.2877	likely_benign	0.2584	benign	0.171	Stabilizing	0.961	D	0.274	neutral	None	None	None	None	N
Q/E	0.0733	likely_benign	0.0725	benign	0.162	Stabilizing	0.789	D	0.269	neutral	N	0.469546783	None	None	N
Q/F	0.6424	likely_pathogenic	0.6004	pathogenic	-0.339	Destabilizing	0.996	D	0.329	neutral	None	None	None	None	N
Q/G	0.2942	likely_benign	0.2557	benign	-0.287	Destabilizing	0.961	D	0.331	neutral	None	None	None	None	N
Q/H	0.1774	likely_benign	0.1567	benign	-0.001	Destabilizing	0.995	D	0.303	neutral	D	0.527461723	None	None	N
Q/I	0.3265	likely_benign	0.3044	benign	0.273	Stabilizing	0.996	D	0.352	neutral	None	None	None	None	N
Q/K	0.0826	likely_benign	0.0768	benign	0.102	Stabilizing	0.017	N	0.139	neutral	N	0.456713559	None	None	N
Q/L	0.1497	likely_benign	0.1417	benign	0.273	Stabilizing	0.948	D	0.331	neutral	N	0.517860805	None	None	N
Q/M	0.3211	likely_benign	0.3139	benign	0.196	Stabilizing	0.996	D	0.304	neutral	None	None	None	None	N
Q/N	0.2314	likely_benign	0.2014	benign	-0.367	Destabilizing	0.961	D	0.271	neutral	None	None	None	None	N
Q/P	0.4393	ambiguous	0.3344	benign	0.174	Stabilizing	0.982	D	0.351	neutral	N	0.515993172	None	None	N
Q/R	0.102	likely_benign	0.0951	benign	0.273	Stabilizing	0.028	N	0.161	neutral	N	0.474069956	None	None	N
Q/S	0.2484	likely_benign	0.2193	benign	-0.348	Destabilizing	0.832	D	0.299	neutral	None	None	None	None	N
Q/T	0.1878	likely_benign	0.1749	benign	-0.2	Destabilizing	0.961	D	0.337	neutral	None	None	None	None	N
Q/V	0.2302	likely_benign	0.2145	benign	0.174	Stabilizing	0.961	D	0.365	neutral	None	None	None	None	N
Q/W	0.5106	ambiguous	0.4689	ambiguous	-0.371	Destabilizing	0.999	D	0.34	neutral	None	None	None	None	N
Q/Y	0.4349	ambiguous	0.388	ambiguous	-0.081	Destabilizing	0.996	D	0.325	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.