TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24748	74467;74468;74469	chr2:178571890;178571889;178571888	chr2:179436617;179436616;179436615
N2AB	23107	69544;69545;69546	chr2:178571890;178571889;178571888	chr2:179436617;179436616;179436615
N2A	22180	66763;66764;66765	chr2:178571890;178571889;178571888	chr2:179436617;179436616;179436615
N2B	15683	47272;47273;47274	chr2:178571890;178571889;178571888	chr2:179436617;179436616;179436615
Novex-1	15808	47647;47648;47649	chr2:178571890;178571889;178571888	chr2:179436617;179436616;179436615
Novex-2	15875	47848;47849;47850	chr2:178571890;178571889;178571888	chr2:179436617;179436616;179436615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-133
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.4719
• 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
T/I	rs768606900	0.226	0.193	D	0.569	0.153	0.227260227426	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/I	rs768606900	0.226	0.193	D	0.569	0.153	0.227260227426	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs768606900	0.226	0.193	D	0.569	0.153	0.227260227426	gnomAD-4.0.0	5.57875E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.62978E-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
T/A	0.0801	likely_benign	0.0761	benign	-0.858	Destabilizing	0.001	N	0.227	neutral	N	0.486795647	None	None	N
T/C	0.2948	likely_benign	0.2823	benign	-0.401	Destabilizing	0.944	D	0.597	neutral	None	None	None	None	N
T/D	0.3402	ambiguous	0.312	benign	-0.487	Destabilizing	0.388	N	0.607	neutral	None	None	None	None	N
T/E	0.2671	likely_benign	0.246	benign	-0.431	Destabilizing	0.241	N	0.588	neutral	None	None	None	None	N
T/F	0.1418	likely_benign	0.135	benign	-0.684	Destabilizing	0.005	N	0.482	neutral	None	None	None	None	N
T/G	0.2345	likely_benign	0.2129	benign	-1.18	Destabilizing	0.241	N	0.596	neutral	None	None	None	None	N
T/H	0.2019	likely_benign	0.1885	benign	-1.381	Destabilizing	0.01	N	0.516	neutral	None	None	None	None	N
T/I	0.0811	likely_benign	0.0764	benign	-0.069	Destabilizing	0.193	N	0.569	neutral	D	0.522170547	None	None	N
T/K	0.2146	likely_benign	0.1993	benign	-0.869	Destabilizing	0.388	N	0.587	neutral	None	None	None	None	N
T/L	0.0719	likely_benign	0.066	benign	-0.069	Destabilizing	0.116	N	0.571	neutral	None	None	None	None	N
T/M	0.0795	likely_benign	0.0762	benign	0.133	Stabilizing	0.818	D	0.61	neutral	None	None	None	None	N
T/N	0.111	likely_benign	0.108	benign	-0.929	Destabilizing	0.193	N	0.567	neutral	N	0.500811751	None	None	N
T/P	0.5915	likely_pathogenic	0.5766	pathogenic	-0.299	Destabilizing	0.773	D	0.62	neutral	D	0.528070266	None	None	N
T/Q	0.2063	likely_benign	0.1915	benign	-0.934	Destabilizing	0.69	D	0.622	neutral	None	None	None	None	N
T/R	0.1894	likely_benign	0.1754	benign	-0.725	Destabilizing	0.69	D	0.621	neutral	None	None	None	None	N
T/S	0.0874	likely_benign	0.0842	benign	-1.166	Destabilizing	0.006	N	0.365	neutral	N	0.436778217	None	None	N
T/V	0.0787	likely_benign	0.0765	benign	-0.299	Destabilizing	0.002	N	0.229	neutral	None	None	None	None	N
T/W	0.5113	ambiguous	0.4848	ambiguous	-0.723	Destabilizing	0.981	D	0.625	neutral	None	None	None	None	N
T/Y	0.2154	likely_benign	0.2144	benign	-0.485	Destabilizing	0.527	D	0.615	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.