TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29036	87331;87332;87333	chr2:178558353;178558352;178558351	chr2:179423080;179423079;179423078
N2AB	27395	82408;82409;82410	chr2:178558353;178558352;178558351	chr2:179423080;179423079;179423078
N2A	26468	79627;79628;79629	chr2:178558353;178558352;178558351	chr2:179423080;179423079;179423078
N2B	19971	60136;60137;60138	chr2:178558353;178558352;178558351	chr2:179423080;179423079;179423078
Novex-1	20096	60511;60512;60513	chr2:178558353;178558352;178558351	chr2:179423080;179423079;179423078
Novex-2	20163	60712;60713;60714	chr2:178558353;178558352;178558351	chr2:179423080;179423079;179423078
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: Fn3-99
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.5565
• 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/N	None	None	0.999	D	0.705	0.346	0.340032825777	gnomAD-4.0.0	6.85198E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99881E-07	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	0.5526	ambiguous	0.5837	pathogenic	-0.385	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
K/C	0.7202	likely_pathogenic	0.7394	pathogenic	-0.492	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/D	0.8365	likely_pathogenic	0.8493	pathogenic	-0.132	Destabilizing	0.999	D	0.734	deleterious	None	None	None	None	N
K/E	0.2777	likely_benign	0.2897	benign	-0.041	Destabilizing	0.99	D	0.687	prob.delet.	N	0.480537768	None	None	N
K/F	0.9147	likely_pathogenic	0.9273	pathogenic	-0.073	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
K/G	0.6261	likely_pathogenic	0.6617	pathogenic	-0.739	Destabilizing	0.999	D	0.686	prob.delet.	None	None	None	None	N
K/H	0.3828	ambiguous	0.4004	ambiguous	-1.068	Destabilizing	1.0	D	0.663	prob.neutral	None	None	None	None	N
K/I	0.6268	likely_pathogenic	0.6525	pathogenic	0.52	Stabilizing	0.978	D	0.761	deleterious	None	None	None	None	N
K/L	0.5746	likely_pathogenic	0.6172	pathogenic	0.52	Stabilizing	0.978	D	0.686	prob.delet.	None	None	None	None	N
K/M	0.391	ambiguous	0.4241	ambiguous	0.347	Stabilizing	0.998	D	0.658	prob.neutral	N	0.487592114	None	None	N
K/N	0.693	likely_pathogenic	0.7275	pathogenic	-0.369	Destabilizing	0.999	D	0.705	prob.delet.	D	0.522368592	None	None	N
K/P	0.9505	likely_pathogenic	0.9543	pathogenic	0.25	Stabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
K/Q	0.1373	likely_benign	0.1443	benign	-0.468	Destabilizing	0.993	D	0.737	deleterious	N	0.503464569	None	None	N
K/R	0.0777	likely_benign	0.0788	benign	-0.581	Destabilizing	0.984	D	0.651	prob.neutral	N	0.488649832	None	None	N
K/S	0.5908	likely_pathogenic	0.6303	pathogenic	-0.979	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
K/T	0.2821	likely_benign	0.3052	benign	-0.691	Destabilizing	0.997	D	0.689	prob.delet.	N	0.488135092	None	None	N
K/V	0.5302	ambiguous	0.5504	ambiguous	0.25	Stabilizing	0.984	D	0.721	deleterious	None	None	None	None	N
K/W	0.8428	likely_pathogenic	0.8602	pathogenic	0.038	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/Y	0.8184	likely_pathogenic	0.8387	pathogenic	0.321	Stabilizing	0.996	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.