TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5966	18121;18122;18123	chr2:178730637;178730636;178730635	chr2:179595364;179595363;179595362
N2AB	5649	17170;17171;17172	chr2:178730637;178730636;178730635	chr2:179595364;179595363;179595362
N2A	4722	14389;14390;14391	chr2:178730637;178730636;178730635	chr2:179595364;179595363;179595362
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-43
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3304
• 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
K/T	rs1469567732	-0.896	0.999	N	0.667	0.501	0.462809833587	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/T	rs1469567732	-0.896	0.999	N	0.667	0.501	0.462809833587	gnomAD-4.0.0	2.73703E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	0	2.69862E-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
K/A	0.5499	ambiguous	0.5574	ambiguous	-0.599	Destabilizing	0.998	D	0.546	neutral	None	None	None	None	N
K/C	0.7775	likely_pathogenic	0.7707	pathogenic	-0.769	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.7348	likely_pathogenic	0.7515	pathogenic	-0.166	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/E	0.3622	ambiguous	0.3811	ambiguous	-0.079	Destabilizing	0.996	D	0.46	neutral	N	0.490788847	None	None	N
K/F	0.8732	likely_pathogenic	0.8871	pathogenic	-0.495	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/G	0.6751	likely_pathogenic	0.6841	pathogenic	-0.929	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
K/H	0.2774	likely_benign	0.2924	benign	-1.325	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.4718	ambiguous	0.5106	ambiguous	0.24	Stabilizing	1.0	D	0.771	deleterious	D	0.52322934	None	None	N
K/L	0.5035	ambiguous	0.5084	ambiguous	0.24	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
K/M	0.3904	ambiguous	0.3998	ambiguous	0.192	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/N	0.5183	ambiguous	0.5407	ambiguous	-0.427	Destabilizing	0.999	D	0.615	neutral	D	0.529037804	None	None	N
K/P	0.9566	likely_pathogenic	0.956	pathogenic	-0.01	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/Q	0.1704	likely_benign	0.1804	benign	-0.603	Destabilizing	0.999	D	0.595	neutral	N	0.418774033	None	None	N
K/R	0.0814	likely_benign	0.0875	benign	-0.528	Destabilizing	0.64	D	0.275	neutral	N	0.423814494	None	None	N
K/S	0.5372	ambiguous	0.5526	ambiguous	-1.127	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
K/T	0.2436	likely_benign	0.2548	benign	-0.842	Destabilizing	0.999	D	0.667	neutral	N	0.492906433	None	None	N
K/V	0.4497	ambiguous	0.4751	ambiguous	-0.01	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/W	0.8329	likely_pathogenic	0.842	pathogenic	-0.338	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
K/Y	0.715	likely_pathogenic	0.725	pathogenic	-0.005	Destabilizing	1.0	D	0.73	prob.delet.	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.