TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29852	89779;89780;89781	chr2:178553346;178553345;178553344	chr2:179418073;179418072;179418071
N2AB	28211	84856;84857;84858	chr2:178553346;178553345;178553344	chr2:179418073;179418072;179418071
N2A	27284	82075;82076;82077	chr2:178553346;178553345;178553344	chr2:179418073;179418072;179418071
N2B	20787	62584;62585;62586	chr2:178553346;178553345;178553344	chr2:179418073;179418072;179418071
Novex-1	20912	62959;62960;62961	chr2:178553346;178553345;178553344	chr2:179418073;179418072;179418071
Novex-2	20979	63160;63161;63162	chr2:178553346;178553345;178553344	chr2:179418073;179418072;179418071
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-147
• Domain position: 11
• Structural Position: 18
• Q(SASA): 0.578
• 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/R	rs771570602	-0.025	0.217	N	0.322	0.132	0.201204373187	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
K/R	rs771570602	-0.025	0.217	N	0.322	0.132	0.201204373187	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
K/A	0.6627	likely_pathogenic	0.5791	pathogenic	-0.05	Destabilizing	0.996	D	0.65	neutral	None	None	None	None	N
K/C	0.8535	likely_pathogenic	0.8223	pathogenic	-0.316	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/D	0.9141	likely_pathogenic	0.8786	pathogenic	0.013	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
K/E	0.4508	ambiguous	0.366	ambiguous	0.044	Stabilizing	0.989	D	0.612	neutral	N	0.50723838	None	None	N
K/F	0.8906	likely_pathogenic	0.8565	pathogenic	-0.126	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/G	0.8074	likely_pathogenic	0.7474	pathogenic	-0.285	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
K/H	0.4352	ambiguous	0.3972	ambiguous	-0.505	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
K/I	0.6266	likely_pathogenic	0.5525	ambiguous	0.501	Stabilizing	0.999	D	0.723	prob.delet.	D	0.526229572	None	None	N
K/L	0.5795	likely_pathogenic	0.5065	ambiguous	0.501	Stabilizing	0.999	D	0.626	neutral	None	None	None	None	N
K/M	0.4543	ambiguous	0.3907	ambiguous	0.174	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
K/N	0.7901	likely_pathogenic	0.7265	pathogenic	0.023	Stabilizing	0.998	D	0.649	neutral	N	0.503448713	None	None	N
K/P	0.8772	likely_pathogenic	0.806	pathogenic	0.347	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	N
K/Q	0.2496	likely_benign	0.2152	benign	-0.1	Destabilizing	0.997	D	0.646	neutral	N	0.500965768	None	None	N
K/R	0.087	likely_benign	0.0821	benign	-0.167	Destabilizing	0.217	N	0.322	neutral	N	0.400302916	None	None	N
K/S	0.7857	likely_pathogenic	0.7221	pathogenic	-0.46	Destabilizing	0.996	D	0.638	neutral	None	None	None	None	N
K/T	0.4374	ambiguous	0.3725	ambiguous	-0.269	Destabilizing	0.998	D	0.633	neutral	N	0.498157537	None	None	N
K/V	0.5401	ambiguous	0.468	ambiguous	0.347	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.886	likely_pathogenic	0.8468	pathogenic	-0.137	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/Y	0.7975	likely_pathogenic	0.7467	pathogenic	0.198	Stabilizing	1.0	D	0.702	prob.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.