TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7050	21373;21374;21375	chr2:178724111;178724110;178724109	chr2:179588838;179588837;179588836
N2AB	6733	20422;20423;20424	chr2:178724111;178724110;178724109	chr2:179588838;179588837;179588836
N2A	5806	17641;17642;17643	chr2:178724111;178724110;178724109	chr2:179588838;179588837;179588836
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-55
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1541
• 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/P	None	None	1.0	N	0.901	0.483	0.65389565194	gnomAD-4.0.0	6.84746E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00041E-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
L/A	0.9026	likely_pathogenic	0.8413	pathogenic	-2.2	Highly Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/C	0.9447	likely_pathogenic	0.9319	pathogenic	-1.313	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/D	0.9968	likely_pathogenic	0.9969	pathogenic	-1.993	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/E	0.9772	likely_pathogenic	0.9772	pathogenic	-1.88	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/F	0.654	likely_pathogenic	0.71	pathogenic	-1.366	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/G	0.9714	likely_pathogenic	0.9629	pathogenic	-2.654	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/H	0.9665	likely_pathogenic	0.9716	pathogenic	-1.991	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/I	0.2879	likely_benign	0.2816	benign	-0.949	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
L/K	0.9658	likely_pathogenic	0.9713	pathogenic	-1.565	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/M	0.3334	likely_benign	0.3213	benign	-0.717	Destabilizing	1.0	D	0.774	deleterious	N	0.486361351	None	None	N
L/N	0.9826	likely_pathogenic	0.983	pathogenic	-1.55	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/P	0.6198	likely_pathogenic	0.5694	pathogenic	-1.34	Destabilizing	1.0	D	0.901	deleterious	N	0.483067001	None	None	N
L/Q	0.9089	likely_pathogenic	0.9147	pathogenic	-1.588	Destabilizing	1.0	D	0.884	deleterious	D	0.528748379	None	None	N
L/R	0.9379	likely_pathogenic	0.9447	pathogenic	-1.109	Destabilizing	1.0	D	0.881	deleterious	N	0.505871185	None	None	N
L/S	0.9795	likely_pathogenic	0.9693	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/T	0.9421	likely_pathogenic	0.9155	pathogenic	-1.998	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/V	0.3909	ambiguous	0.3317	benign	-1.34	Destabilizing	0.999	D	0.529	neutral	N	0.488234229	None	None	N
L/W	0.9134	likely_pathogenic	0.9308	pathogenic	-1.624	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/Y	0.9698	likely_pathogenic	0.9752	pathogenic	-1.37	Destabilizing	1.0	D	0.853	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.