TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32169	96730;96731;96732	chr2:178543468;178543467;178543466	chr2:179408195;179408194;179408193
N2AB	30528	91807;91808;91809	chr2:178543468;178543467;178543466	chr2:179408195;179408194;179408193
N2A	29601	89026;89027;89028	chr2:178543468;178543467;178543466	chr2:179408195;179408194;179408193
N2B	23104	69535;69536;69537	chr2:178543468;178543467;178543466	chr2:179408195;179408194;179408193
Novex-1	23229	69910;69911;69912	chr2:178543468;178543467;178543466	chr2:179408195;179408194;179408193
Novex-2	23296	70111;70112;70113	chr2:178543468;178543467;178543466	chr2:179408195;179408194;179408193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-122
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.1046
• 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
L/F	None	None	1.0	D	0.868	0.71	0.842498291583	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
L/A	0.8931	likely_pathogenic	0.8848	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/C	0.8764	likely_pathogenic	0.8721	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9987	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/E	0.9953	likely_pathogenic	0.994	pathogenic	-1.931	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/F	0.8363	likely_pathogenic	0.8317	pathogenic	-1.649	Destabilizing	1.0	D	0.868	deleterious	D	0.631080202	None	None	N
L/G	0.9817	likely_pathogenic	0.9787	pathogenic	-2.973	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9909	likely_pathogenic	0.9876	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.813	deleterious	D	0.647906781	None	None	N
L/I	0.2806	likely_benign	0.2979	benign	-0.904	Destabilizing	0.995	D	0.839	deleterious	D	0.630071181	None	None	N
L/K	0.9923	likely_pathogenic	0.9913	pathogenic	-1.718	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/M	0.3933	ambiguous	0.418	ambiguous	-1.069	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/N	0.9894	likely_pathogenic	0.9866	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/P	0.9884	likely_pathogenic	0.984	pathogenic	-1.394	Destabilizing	1.0	D	0.858	deleterious	D	0.647906781	None	None	N
L/Q	0.9807	likely_pathogenic	0.9763	pathogenic	-1.908	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/R	0.984	likely_pathogenic	0.9809	pathogenic	-1.476	Destabilizing	1.0	D	0.851	deleterious	D	0.63188742	None	None	N
L/S	0.9855	likely_pathogenic	0.9821	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/T	0.9044	likely_pathogenic	0.8942	pathogenic	-2.494	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/V	0.2806	likely_benign	0.3134	benign	-1.394	Destabilizing	0.996	D	0.848	deleterious	D	0.577480528	None	None	N
L/W	0.9834	likely_pathogenic	0.9799	pathogenic	-1.868	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/Y	0.9863	likely_pathogenic	0.9855	pathogenic	-1.586	Destabilizing	0.999	D	0.827	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.