TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2800	8623;8624;8625	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028
N2AB	2800	8623;8624;8625	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028
N2A	2800	8623;8624;8625	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028
N2B	2754	8485;8486;8487	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028
Novex-1	2754	8485;8486;8487	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028
Novex-2	2754	8485;8486;8487	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028
Novex-3	2800	8623;8624;8625	chr2:178770303;178770302;178770301	chr2:179635030;179635029;179635028

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-18
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4153
• 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	0.56	0.405	0.40218521252	gnomAD-4.0.0	1.59048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85642E-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	0.9081	likely_pathogenic	0.8758	pathogenic	-0.103	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
K/C	0.9649	likely_pathogenic	0.9541	pathogenic	-0.358	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/D	0.976	likely_pathogenic	0.9661	pathogenic	0.192	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/E	0.8341	likely_pathogenic	0.77	pathogenic	0.248	Stabilizing	0.999	D	0.621	neutral	N	0.512590353	None	None	N
K/F	0.9815	likely_pathogenic	0.9714	pathogenic	-0.058	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
K/G	0.9524	likely_pathogenic	0.9338	pathogenic	-0.376	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.756	likely_pathogenic	0.7055	pathogenic	-0.63	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/I	0.9056	likely_pathogenic	0.8664	pathogenic	0.557	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/L	0.8417	likely_pathogenic	0.7975	pathogenic	0.557	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/M	0.7095	likely_pathogenic	0.6586	pathogenic	0.197	Stabilizing	1.0	D	0.717	prob.delet.	D	0.581083999	None	None	N
K/N	0.9217	likely_pathogenic	0.9004	pathogenic	-0.022	Destabilizing	1.0	D	0.752	deleterious	N	0.506447159	None	None	N
K/P	0.8796	likely_pathogenic	0.8664	pathogenic	0.367	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/Q	0.4966	ambiguous	0.4306	ambiguous	-0.105	Destabilizing	1.0	D	0.724	prob.delet.	N	0.511268854	None	None	N
K/R	0.159	likely_benign	0.1478	benign	-0.233	Destabilizing	0.999	D	0.56	neutral	N	0.505827063	None	None	N
K/S	0.9443	likely_pathogenic	0.9236	pathogenic	-0.56	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/T	0.7954	likely_pathogenic	0.7478	pathogenic	-0.328	Destabilizing	1.0	D	0.783	deleterious	N	0.512080512	None	None	N
K/V	0.8822	likely_pathogenic	0.8378	pathogenic	0.367	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
K/W	0.9776	likely_pathogenic	0.9676	pathogenic	-0.036	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/Y	0.9292	likely_pathogenic	0.9088	pathogenic	0.292	Stabilizing	1.0	D	0.751	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.