TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27902	83929;83930;83931	chr2:178562428;178562427;178562426	chr2:179427155;179427154;179427153
N2AB	26261	79006;79007;79008	chr2:178562428;178562427;178562426	chr2:179427155;179427154;179427153
N2A	25334	76225;76226;76227	chr2:178562428;178562427;178562426	chr2:179427155;179427154;179427153
N2B	18837	56734;56735;56736	chr2:178562428;178562427;178562426	chr2:179427155;179427154;179427153
Novex-1	18962	57109;57110;57111	chr2:178562428;178562427;178562426	chr2:179427155;179427154;179427153
Novex-2	19029	57310;57311;57312	chr2:178562428;178562427;178562426	chr2:179427155;179427154;179427153
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-91
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.0961
• 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
M/I	None	None	0.918	N	0.605	0.28	0.534955811369	gnomAD-4.0.0	1.59314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86018E-06	0	0
M/T	None	None	0.9	N	0.588	0.358	0.635205937663	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85995E-06	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
M/A	0.8396	likely_pathogenic	0.8621	pathogenic	-1.976	Destabilizing	0.942	D	0.54	neutral	None	None	None	None	N
M/C	0.8427	likely_pathogenic	0.8508	pathogenic	-1.705	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
M/D	0.9958	likely_pathogenic	0.996	pathogenic	-1.453	Destabilizing	0.988	D	0.735	prob.delet.	None	None	None	None	N
M/E	0.9434	likely_pathogenic	0.9518	pathogenic	-1.188	Destabilizing	0.828	D	0.627	neutral	None	None	None	None	N
M/F	0.47	ambiguous	0.4876	ambiguous	-0.589	Destabilizing	0.976	D	0.617	neutral	None	None	None	None	N
M/G	0.9293	likely_pathogenic	0.9336	pathogenic	-2.502	Highly Destabilizing	0.975	D	0.669	neutral	None	None	None	None	N
M/H	0.8817	likely_pathogenic	0.8929	pathogenic	-2.222	Highly Destabilizing	0.992	D	0.709	prob.delet.	None	None	None	None	N
M/I	0.7194	likely_pathogenic	0.7665	pathogenic	-0.455	Destabilizing	0.918	D	0.605	neutral	N	0.495140582	None	None	N
M/K	0.462	ambiguous	0.5227	ambiguous	-0.852	Destabilizing	0.735	D	0.572	neutral	N	0.47430395	None	None	N
M/L	0.3047	likely_benign	0.3529	ambiguous	-0.455	Destabilizing	0.499	N	0.454	neutral	N	0.515745141	None	None	N
M/N	0.9382	likely_pathogenic	0.945	pathogenic	-1.309	Destabilizing	0.977	D	0.701	prob.neutral	None	None	None	None	N
M/P	0.9991	likely_pathogenic	0.9992	pathogenic	-0.945	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
M/Q	0.6239	likely_pathogenic	0.6511	pathogenic	-0.9	Destabilizing	0.943	D	0.612	neutral	None	None	None	None	N
M/R	0.5505	ambiguous	0.6163	pathogenic	-1.2	Destabilizing	0.036	N	0.386	neutral	N	0.46889813	None	None	N
M/S	0.8718	likely_pathogenic	0.8788	pathogenic	-1.912	Destabilizing	0.975	D	0.604	neutral	None	None	None	None	N
M/T	0.7668	likely_pathogenic	0.8027	pathogenic	-1.496	Destabilizing	0.9	D	0.588	neutral	N	0.473050625	None	None	N
M/V	0.3003	likely_benign	0.3387	benign	-0.945	Destabilizing	0.912	D	0.577	neutral	N	0.509819246	None	None	N
M/W	0.8581	likely_pathogenic	0.8726	pathogenic	-0.897	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
M/Y	0.7038	likely_pathogenic	0.7225	pathogenic	-0.844	Destabilizing	0.998	D	0.66	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.