TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25738	77437;77438;77439	chr2:178568920;178568919;178568918	chr2:179433647;179433646;179433645
N2AB	24097	72514;72515;72516	chr2:178568920;178568919;178568918	chr2:179433647;179433646;179433645
N2A	23170	69733;69734;69735	chr2:178568920;178568919;178568918	chr2:179433647;179433646;179433645
N2B	16673	50242;50243;50244	chr2:178568920;178568919;178568918	chr2:179433647;179433646;179433645
Novex-1	16798	50617;50618;50619	chr2:178568920;178568919;178568918	chr2:179433647;179433646;179433645
Novex-2	16865	50818;50819;50820	chr2:178568920;178568919;178568918	chr2:179433647;179433646;179433645
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: Fn3-75
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1459
• 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/K	None	None	0.984	N	0.431	0.208	0.1749357433	gnomAD-4.0.0	6.8438E-07	None	None	None	None	N	None	2.99025E-05	0	None	0	0	None	0	0	0	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
Q/A	0.3944	ambiguous	0.4114	ambiguous	-1.045	Destabilizing	0.318	N	0.203	neutral	None	None	None	None	N
Q/C	0.7463	likely_pathogenic	0.7467	pathogenic	-0.427	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
Q/D	0.9259	likely_pathogenic	0.934	pathogenic	-1.408	Destabilizing	0.993	D	0.397	neutral	None	None	None	None	N
Q/E	0.1985	likely_benign	0.2008	benign	-1.196	Destabilizing	0.97	D	0.39	neutral	N	0.494988654	None	None	N
Q/F	0.9179	likely_pathogenic	0.9294	pathogenic	-0.692	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
Q/G	0.6104	likely_pathogenic	0.6293	pathogenic	-1.467	Destabilizing	0.99	D	0.418	neutral	None	None	None	None	N
Q/H	0.5965	likely_pathogenic	0.6051	pathogenic	-1.199	Destabilizing	0.189	N	0.297	neutral	N	0.486576658	None	None	N
Q/I	0.7017	likely_pathogenic	0.712	pathogenic	0.087	Stabilizing	0.999	D	0.569	neutral	None	None	None	None	N
Q/K	0.1368	likely_benign	0.1363	benign	-0.337	Destabilizing	0.984	D	0.431	neutral	N	0.428494303	None	None	N
Q/L	0.2337	likely_benign	0.2505	benign	0.087	Stabilizing	0.987	D	0.47	neutral	N	0.516865436	None	None	N
Q/M	0.4511	ambiguous	0.4729	ambiguous	0.501	Stabilizing	1.0	D	0.445	neutral	None	None	None	None	N
Q/N	0.7266	likely_pathogenic	0.7413	pathogenic	-1.133	Destabilizing	0.987	D	0.391	neutral	None	None	None	None	N
Q/P	0.9325	likely_pathogenic	0.929	pathogenic	-0.262	Destabilizing	0.991	D	0.444	neutral	N	0.509200364	None	None	N
Q/R	0.1559	likely_benign	0.1583	benign	-0.424	Destabilizing	0.99	D	0.414	neutral	N	0.4483495	None	None	N
Q/S	0.635	likely_pathogenic	0.6605	pathogenic	-1.364	Destabilizing	0.981	D	0.393	neutral	None	None	None	None	N
Q/T	0.5701	likely_pathogenic	0.571	pathogenic	-0.944	Destabilizing	0.906	D	0.435	neutral	None	None	None	None	N
Q/V	0.4973	ambiguous	0.5117	ambiguous	-0.262	Destabilizing	0.967	D	0.455	neutral	None	None	None	None	N
Q/W	0.8902	likely_pathogenic	0.9085	pathogenic	-0.609	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
Q/Y	0.8002	likely_pathogenic	0.8262	pathogenic	-0.282	Destabilizing	0.998	D	0.469	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.