TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16911	50956;50957;50958	chr2:178611498;178611497;178611496	chr2:179476225;179476224;179476223
N2AB	15270	46033;46034;46035	chr2:178611498;178611497;178611496	chr2:179476225;179476224;179476223
N2A	14343	43252;43253;43254	chr2:178611498;178611497;178611496	chr2:179476225;179476224;179476223
N2B	7846	23761;23762;23763	chr2:178611498;178611497;178611496	chr2:179476225;179476224;179476223
Novex-1	7971	24136;24137;24138	chr2:178611498;178611497;178611496	chr2:179476225;179476224;179476223
Novex-2	8038	24337;24338;24339	chr2:178611498;178611497;178611496	chr2:179476225;179476224;179476223
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: Fn3-11
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.6245
• 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	None	None	0.999	N	0.561	0.291	0.380052290102	gnomAD-4.0.0	1.59291E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86143E-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	0.4614	ambiguous	0.609	pathogenic	-0.522	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/C	0.6416	likely_pathogenic	0.7788	pathogenic	-0.578	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/D	0.7571	likely_pathogenic	0.8473	pathogenic	-0.192	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/E	0.3514	ambiguous	0.4791	ambiguous	-0.058	Destabilizing	0.999	D	0.592	neutral	N	0.423021345	None	None	N
K/F	0.8205	likely_pathogenic	0.9056	pathogenic	-0.148	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/G	0.6507	likely_pathogenic	0.7846	pathogenic	-0.878	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
K/H	0.2773	likely_benign	0.36	ambiguous	-0.964	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/I	0.4212	ambiguous	0.5497	ambiguous	0.403	Stabilizing	1.0	D	0.765	deleterious	N	0.480649981	None	None	N
K/L	0.439	ambiguous	0.5628	ambiguous	0.403	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	N
K/M	0.2976	likely_benign	0.4186	ambiguous	-0.01	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/N	0.501	ambiguous	0.6142	pathogenic	-0.488	Destabilizing	1.0	D	0.745	deleterious	N	0.477940562	None	None	N
K/P	0.9452	likely_pathogenic	0.9629	pathogenic	0.123	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/Q	0.1475	likely_benign	0.1934	benign	-0.443	Destabilizing	1.0	D	0.726	prob.delet.	N	0.474256432	None	None	N
K/R	0.083	likely_benign	0.0961	benign	-0.424	Destabilizing	0.999	D	0.561	neutral	N	0.432119043	None	None	N
K/S	0.4787	ambiguous	0.6075	pathogenic	-1.044	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/T	0.1793	likely_benign	0.2579	benign	-0.703	Destabilizing	1.0	D	0.727	prob.delet.	N	0.430128947	None	None	N
K/V	0.376	ambiguous	0.497	ambiguous	0.123	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/W	0.8156	likely_pathogenic	0.8951	pathogenic	-0.106	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/Y	0.6636	likely_pathogenic	0.7899	pathogenic	0.171	Stabilizing	1.0	D	0.743	deleterious	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.