TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7614	23065;23066;23067	chr2:178721179;178721178;178721177	chr2:179585906;179585905;179585904
N2AB	7297	22114;22115;22116	chr2:178721179;178721178;178721177	chr2:179585906;179585905;179585904
N2A	6370	19333;19334;19335	chr2:178721179;178721178;178721177	chr2:179585906;179585905;179585904
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: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-61
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2127
• 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/S	None	None	0.307	N	0.401	0.283	0.662284845153	gnomAD-4.0.0	2.7597E-06	None	None	None	None	N	None	1.21087E-04	0	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	0.6509	likely_pathogenic	0.5684	pathogenic	-2.241	Highly Destabilizing	0.168	N	0.269	neutral	None	None	None	None	N
L/C	0.9251	likely_pathogenic	0.8865	pathogenic	-1.426	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	N
L/D	0.9923	likely_pathogenic	0.9879	pathogenic	-1.796	Destabilizing	0.981	D	0.655	neutral	None	None	None	None	N
L/E	0.9562	likely_pathogenic	0.9402	pathogenic	-1.725	Destabilizing	0.917	D	0.629	neutral	None	None	None	None	N
L/F	0.6796	likely_pathogenic	0.627	pathogenic	-1.531	Destabilizing	0.941	D	0.559	neutral	N	0.477055734	None	None	N
L/G	0.9277	likely_pathogenic	0.9013	pathogenic	-2.661	Highly Destabilizing	0.938	D	0.557	neutral	None	None	None	None	N
L/H	0.9544	likely_pathogenic	0.9313	pathogenic	-1.905	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
L/I	0.2111	likely_benign	0.174	benign	-1.103	Destabilizing	0.143	N	0.457	neutral	N	0.475218855	None	None	N
L/K	0.9534	likely_pathogenic	0.9363	pathogenic	-1.567	Destabilizing	0.307	N	0.583	neutral	None	None	None	None	N
L/M	0.2338	likely_benign	0.1848	benign	-0.834	Destabilizing	0.14	N	0.304	neutral	None	None	None	None	N
L/N	0.9515	likely_pathogenic	0.9265	pathogenic	-1.447	Destabilizing	0.981	D	0.667	neutral	None	None	None	None	N
L/P	0.326	likely_benign	0.2535	benign	-1.455	Destabilizing	0.019	N	0.393	neutral	None	None	None	None	N
L/Q	0.8526	likely_pathogenic	0.7973	pathogenic	-1.553	Destabilizing	0.978	D	0.629	neutral	None	None	None	None	N
L/R	0.9218	likely_pathogenic	0.8943	pathogenic	-1.026	Destabilizing	0.977	D	0.633	neutral	None	None	None	None	N
L/S	0.9239	likely_pathogenic	0.8806	pathogenic	-2.157	Highly Destabilizing	0.307	N	0.401	neutral	N	0.497882241	None	None	N
L/T	0.677	likely_pathogenic	0.5805	pathogenic	-1.956	Destabilizing	0.694	D	0.475	neutral	None	None	None	None	N
L/V	0.1998	likely_benign	0.1629	benign	-1.455	Destabilizing	0.083	N	0.419	neutral	N	0.475725834	None	None	N
L/W	0.8979	likely_pathogenic	0.8717	pathogenic	-1.674	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
L/Y	0.9628	likely_pathogenic	0.9512	pathogenic	-1.465	Destabilizing	0.833	D	0.631	neutral	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.