TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9596	29011;29012;29013	chr2:178707781;178707780;178707779	chr2:179572508;179572507;179572506
N2AB	9279	28060;28061;28062	chr2:178707781;178707780;178707779	chr2:179572508;179572507;179572506
N2A	8352	25279;25280;25281	chr2:178707781;178707780;178707779	chr2:179572508;179572507;179572506
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-82
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1139
• 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	rs2076095126	None	0.971	None	0.646	0.245	0.383256108077	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs2076095126	None	0.971	None	0.646	0.245	0.383256108077	gnomAD-4.0.0	6.44154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.20583E-05	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
L/A	0.7341	likely_pathogenic	0.7471	pathogenic	-2.094	Highly Destabilizing	0.754	D	0.562	neutral	None	None	None	None	N
L/C	0.8423	likely_pathogenic	0.8618	pathogenic	-1.362	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
L/D	0.9911	likely_pathogenic	0.9915	pathogenic	-1.549	Destabilizing	0.956	D	0.789	deleterious	None	None	None	None	N
L/E	0.9536	likely_pathogenic	0.9553	pathogenic	-1.441	Destabilizing	0.956	D	0.811	deleterious	None	None	None	None	N
L/F	0.5527	ambiguous	0.5325	ambiguous	-1.323	Destabilizing	0.971	D	0.646	neutral	None	None	None	None	N
L/G	0.9199	likely_pathogenic	0.9189	pathogenic	-2.534	Highly Destabilizing	0.956	D	0.801	deleterious	None	None	None	None	N
L/H	0.9171	likely_pathogenic	0.922	pathogenic	-1.816	Destabilizing	0.997	D	0.794	deleterious	None	None	None	None	N
L/I	0.171	likely_benign	0.166	benign	-0.89	Destabilizing	0.698	D	0.501	neutral	None	None	None	None	N
L/K	0.9421	likely_pathogenic	0.9535	pathogenic	-1.29	Destabilizing	0.956	D	0.736	prob.delet.	None	None	None	None	N
L/M	0.2432	likely_benign	0.2431	benign	-0.775	Destabilizing	0.978	D	0.648	neutral	None	None	None	None	N
L/N	0.9465	likely_pathogenic	0.9538	pathogenic	-1.26	Destabilizing	0.978	D	0.814	deleterious	None	None	None	None	N
L/P	0.5509	ambiguous	0.6325	pathogenic	-1.265	Destabilizing	0.032	N	0.585	neutral	None	None	None	None	N
L/Q	0.8276	likely_pathogenic	0.835	pathogenic	-1.304	Destabilizing	0.978	D	0.747	deleterious	None	None	None	None	N
L/R	0.8963	likely_pathogenic	0.9021	pathogenic	-0.904	Destabilizing	0.971	D	0.739	prob.delet.	None	None	None	None	N
L/S	0.905	likely_pathogenic	0.9036	pathogenic	-2.029	Highly Destabilizing	0.956	D	0.723	prob.delet.	None	None	None	None	N
L/T	0.7667	likely_pathogenic	0.7803	pathogenic	-1.788	Destabilizing	0.956	D	0.702	prob.neutral	None	None	None	None	N
L/V	0.1992	likely_benign	0.1956	benign	-1.265	Destabilizing	0.058	N	0.393	neutral	None	None	None	None	N
L/W	0.9044	likely_pathogenic	0.9006	pathogenic	-1.499	Destabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
L/Y	0.9482	likely_pathogenic	0.9468	pathogenic	-1.242	Destabilizing	0.993	D	0.724	prob.delet.	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.