TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5444	16555;16556;16557	chr2:178732846;178732845;178732844	chr2:179597573;179597572;179597571
N2AB	5127	15604;15605;15606	chr2:178732846;178732845;178732844	chr2:179597573;179597572;179597571
N2A	4200	12823;12824;12825	chr2:178732846;178732845;178732844	chr2:179597573;179597572;179597571
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-37
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.124
• 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/M	None	None	0.999	N	0.805	0.356	0.59581446357	gnomAD-4.0.0	6.85438E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00872E-07	0	0
L/P	rs1396279222	-1.812	1.0	D	0.897	0.659	0.883428530414	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
L/P	rs1396279222	-1.812	1.0	D	0.897	0.659	0.883428530414	gnomAD-4.0.0	1.60205E-06	None	None	None	None	N	None	0	2.2998E-05	None	0	0	None	0	0	0	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	0.8478	likely_pathogenic	0.8556	pathogenic	-2.636	Highly Destabilizing	0.994	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.8316	likely_pathogenic	0.8388	pathogenic	-1.884	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/D	0.9982	likely_pathogenic	0.9986	pathogenic	-2.515	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/E	0.9882	likely_pathogenic	0.9894	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/F	0.3439	ambiguous	0.3963	ambiguous	-1.656	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
L/G	0.9743	likely_pathogenic	0.9785	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/H	0.9602	likely_pathogenic	0.9628	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/I	0.1264	likely_benign	0.1232	benign	-1.15	Destabilizing	0.833	D	0.367	neutral	None	None	None	None	N
L/K	0.9782	likely_pathogenic	0.9797	pathogenic	-1.967	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/M	0.204	likely_benign	0.2159	benign	-0.985	Destabilizing	0.999	D	0.805	deleterious	N	0.483282792	None	None	N
L/N	0.9849	likely_pathogenic	0.9868	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/P	0.99	likely_pathogenic	0.9921	pathogenic	-1.623	Destabilizing	1.0	D	0.897	deleterious	D	0.551358172	None	None	N
L/Q	0.937	likely_pathogenic	0.9372	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.551358172	None	None	N
L/R	0.9504	likely_pathogenic	0.9525	pathogenic	-1.543	Destabilizing	1.0	D	0.892	deleterious	D	0.551358172	None	None	N
L/S	0.9648	likely_pathogenic	0.9692	pathogenic	-2.909	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/T	0.9034	likely_pathogenic	0.9095	pathogenic	-2.586	Highly Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
L/V	0.1191	likely_benign	0.1152	benign	-1.623	Destabilizing	0.962	D	0.654	neutral	N	0.472764817	None	None	N
L/W	0.8613	likely_pathogenic	0.8816	pathogenic	-1.937	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/Y	0.8743	likely_pathogenic	0.895	pathogenic	-1.699	Destabilizing	1.0	D	0.855	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.