TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6234	18925;18926;18927	chr2:178729456;178729455;178729454	chr2:179594183;179594182;179594181
N2AB	5917	17974;17975;17976	chr2:178729456;178729455;178729454	chr2:179594183;179594182;179594181
N2A	4990	15193;15194;15195	chr2:178729456;178729455;178729454	chr2:179594183;179594182;179594181
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-46
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1507
• 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/Q	None	None	0.468	N	0.659	0.391	0.184867976434	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	None	0	0	0	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	0.9193	likely_pathogenic	0.9434	pathogenic	-1.245	Destabilizing	0.399	N	0.518	neutral	None	None	None	None	N
K/C	0.8371	likely_pathogenic	0.8835	pathogenic	-1.241	Destabilizing	0.982	D	0.845	deleterious	None	None	None	None	N
K/D	0.983	likely_pathogenic	0.9889	pathogenic	-1.034	Destabilizing	0.7	D	0.779	deleterious	None	None	None	None	N
K/E	0.8083	likely_pathogenic	0.8711	pathogenic	-0.789	Destabilizing	0.201	N	0.457	neutral	D	0.523689632	None	None	N
K/F	0.9181	likely_pathogenic	0.9437	pathogenic	-0.718	Destabilizing	0.947	D	0.843	deleterious	None	None	None	None	N
K/G	0.9392	likely_pathogenic	0.9602	pathogenic	-1.719	Destabilizing	0.7	D	0.735	prob.delet.	None	None	None	None	N
K/H	0.4421	ambiguous	0.4847	ambiguous	-1.927	Destabilizing	0.947	D	0.791	deleterious	None	None	None	None	N
K/I	0.8357	likely_pathogenic	0.8796	pathogenic	0.062	Stabilizing	0.826	D	0.855	deleterious	None	None	None	None	N
K/L	0.7119	likely_pathogenic	0.7884	pathogenic	0.062	Stabilizing	0.7	D	0.735	prob.delet.	None	None	None	None	N
K/M	0.6664	likely_pathogenic	0.728	pathogenic	-0.111	Destabilizing	0.976	D	0.779	deleterious	N	0.516852777	None	None	N
K/N	0.9245	likely_pathogenic	0.9421	pathogenic	-1.309	Destabilizing	0.638	D	0.667	neutral	N	0.502863126	None	None	N
K/P	0.9933	likely_pathogenic	0.9946	pathogenic	-0.348	Destabilizing	0.826	D	0.792	deleterious	None	None	None	None	N
K/Q	0.3664	ambiguous	0.4278	ambiguous	-1.103	Destabilizing	0.468	N	0.659	neutral	N	0.516345798	None	None	N
K/R	0.0763	likely_benign	0.0854	benign	-0.888	Destabilizing	0.002	N	0.251	neutral	N	0.48955583	None	None	N
K/S	0.9433	likely_pathogenic	0.9623	pathogenic	-1.989	Destabilizing	0.399	N	0.542	neutral	None	None	None	None	N
K/T	0.8967	likely_pathogenic	0.9309	pathogenic	-1.478	Destabilizing	0.638	D	0.732	prob.delet.	D	0.534703543	None	None	N
K/V	0.8136	likely_pathogenic	0.8651	pathogenic	-0.348	Destabilizing	0.7	D	0.807	deleterious	None	None	None	None	N
K/W	0.8349	likely_pathogenic	0.8773	pathogenic	-0.648	Destabilizing	0.982	D	0.811	deleterious	None	None	None	None	N
K/Y	0.7766	likely_pathogenic	0.8214	pathogenic	-0.315	Destabilizing	0.826	D	0.843	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.