TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32994	99205;99206;99207	chr2:178538955;178538954;178538953	chr2:179403682;179403681;179403680
N2AB	31353	94282;94283;94284	chr2:178538955;178538954;178538953	chr2:179403682;179403681;179403680
N2A	30426	91501;91502;91503	chr2:178538955;178538954;178538953	chr2:179403682;179403681;179403680
N2B	23929	72010;72011;72012	chr2:178538955;178538954;178538953	chr2:179403682;179403681;179403680
Novex-1	24054	72385;72386;72387	chr2:178538955;178538954;178538953	chr2:179403682;179403681;179403680
Novex-2	24121	72586;72587;72588	chr2:178538955;178538954;178538953	chr2:179403682;179403681;179403680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-128
• Domain position: 99
• Structural Position: 132
• Q(SASA): 0.9634
• 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
D/E	None	None	0.999	N	0.555	0.247	0.242244723065	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.6983	likely_pathogenic	0.7105	pathogenic	-0.209	Destabilizing	1.0	D	0.799	deleterious	N	0.493348284	None	None	N
D/C	0.9593	likely_pathogenic	0.9629	pathogenic	-0.035	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
D/E	0.5687	likely_pathogenic	0.5917	pathogenic	-0.274	Destabilizing	0.999	D	0.555	neutral	N	0.478880264	None	None	N
D/F	0.916	likely_pathogenic	0.9057	pathogenic	-0.215	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
D/G	0.8049	likely_pathogenic	0.8263	pathogenic	-0.382	Destabilizing	1.0	D	0.841	deleterious	N	0.495753871	None	None	N
D/H	0.832	likely_pathogenic	0.8544	pathogenic	0.048	Stabilizing	1.0	D	0.902	deleterious	N	0.467437856	None	None	N
D/I	0.8854	likely_pathogenic	0.8695	pathogenic	0.19	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
D/K	0.9453	likely_pathogenic	0.9438	pathogenic	0.256	Stabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
D/L	0.7891	likely_pathogenic	0.7866	pathogenic	0.19	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/M	0.9458	likely_pathogenic	0.9441	pathogenic	0.217	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/N	0.3738	ambiguous	0.4205	ambiguous	0.041	Stabilizing	1.0	D	0.857	deleterious	N	0.488385181	None	None	N
D/P	0.9189	likely_pathogenic	0.9374	pathogenic	0.078	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
D/Q	0.9198	likely_pathogenic	0.9223	pathogenic	0.061	Stabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
D/R	0.9616	likely_pathogenic	0.9596	pathogenic	0.451	Stabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
D/S	0.552	ambiguous	0.5933	pathogenic	-0.077	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
D/T	0.8316	likely_pathogenic	0.8167	pathogenic	0.053	Stabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
D/V	0.7648	likely_pathogenic	0.7368	pathogenic	0.078	Stabilizing	1.0	D	0.847	deleterious	N	0.48690801	None	None	N
D/W	0.9891	likely_pathogenic	0.9885	pathogenic	-0.122	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/Y	0.604	likely_pathogenic	0.5788	pathogenic	0.007	Stabilizing	1.0	D	0.868	deleterious	N	0.470071203	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.