TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32338	97237;97238;97239	chr2:178542842;178542841;178542840	chr2:179407569;179407568;179407567
N2AB	30697	92314;92315;92316	chr2:178542842;178542841;178542840	chr2:179407569;179407568;179407567
N2A	29770	89533;89534;89535	chr2:178542842;178542841;178542840	chr2:179407569;179407568;179407567
N2B	23273	70042;70043;70044	chr2:178542842;178542841;178542840	chr2:179407569;179407568;179407567
Novex-1	23398	70417;70418;70419	chr2:178542842;178542841;178542840	chr2:179407569;179407568;179407567
Novex-2	23465	70618;70619;70620	chr2:178542842;178542841;178542840	chr2:179407569;179407568;179407567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-154
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.4237
• Predicted PPI site: I

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
A/G	None	None	0.946	N	0.658	0.322	0.370424759081	gnomAD-4.0.0	2.05258E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79891E-06	0	1.65651E-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
A/C	0.4088	ambiguous	0.385	ambiguous	-0.963	Destabilizing	0.034	N	0.381	neutral	None	None	None	None	I
A/D	0.8183	likely_pathogenic	0.8153	pathogenic	-1.09	Destabilizing	0.995	D	0.859	deleterious	N	0.493309077	None	None	I
A/E	0.7018	likely_pathogenic	0.7027	pathogenic	-1.108	Destabilizing	0.988	D	0.767	deleterious	None	None	None	None	I
A/F	0.5001	ambiguous	0.4682	ambiguous	-0.963	Destabilizing	0.976	D	0.859	deleterious	None	None	None	None	I
A/G	0.252	likely_benign	0.2246	benign	-1.142	Destabilizing	0.946	D	0.658	neutral	N	0.511990839	None	None	I
A/H	0.7772	likely_pathogenic	0.7697	pathogenic	-1.358	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	I
A/I	0.1819	likely_benign	0.1858	benign	-0.261	Destabilizing	0.851	D	0.747	deleterious	None	None	None	None	I
A/K	0.7963	likely_pathogenic	0.7995	pathogenic	-1.224	Destabilizing	0.988	D	0.769	deleterious	None	None	None	None	I
A/L	0.2135	likely_benign	0.2242	benign	-0.261	Destabilizing	0.702	D	0.708	prob.delet.	None	None	None	None	I
A/M	0.2809	likely_benign	0.289	benign	-0.272	Destabilizing	0.988	D	0.757	deleterious	None	None	None	None	I
A/N	0.6178	likely_pathogenic	0.6304	pathogenic	-0.958	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	I
A/P	0.2292	likely_benign	0.2745	benign	-0.42	Destabilizing	0.995	D	0.767	deleterious	N	0.493135719	None	None	I
A/Q	0.6633	likely_pathogenic	0.6725	pathogenic	-1.074	Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	I
A/R	0.7346	likely_pathogenic	0.7398	pathogenic	-0.928	Destabilizing	0.988	D	0.762	deleterious	None	None	None	None	I
A/S	0.1442	likely_benign	0.1415	benign	-1.324	Destabilizing	0.946	D	0.658	neutral	N	0.468450705	None	None	I
A/T	0.0998	likely_benign	0.1064	benign	-1.235	Destabilizing	0.896	D	0.657	neutral	N	0.463159529	None	None	I
A/V	0.0882	likely_benign	0.0899	benign	-0.42	Destabilizing	0.011	N	0.324	neutral	N	0.372811591	None	None	I
A/W	0.8926	likely_pathogenic	0.8797	pathogenic	-1.33	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	I
A/Y	0.6859	likely_pathogenic	0.6724	pathogenic	-0.906	Destabilizing	0.988	D	0.863	deleterious	None	None	None	None	I

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.