TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27815	83668;83669;83670	chr2:178562689;178562688;178562687	chr2:179427416;179427415;179427414
N2AB	26174	78745;78746;78747	chr2:178562689;178562688;178562687	chr2:179427416;179427415;179427414
N2A	25247	75964;75965;75966	chr2:178562689;178562688;178562687	chr2:179427416;179427415;179427414
N2B	18750	56473;56474;56475	chr2:178562689;178562688;178562687	chr2:179427416;179427415;179427414
Novex-1	18875	56848;56849;56850	chr2:178562689;178562688;178562687	chr2:179427416;179427415;179427414
Novex-2	18942	57049;57050;57051	chr2:178562689;178562688;178562687	chr2:179427416;179427415;179427414
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: Fn3-90
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3615
• 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	None	None	0.006	N	0.241	0.163	0.314716216878	gnomAD-4.0.0	1.6372E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91753E-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	0.0719	likely_benign	0.0777	benign	-0.669	Destabilizing	0.026	N	0.337	neutral	N	0.508533954	None	None	N
T/C	0.4264	ambiguous	0.4226	ambiguous	-0.41	Destabilizing	0.993	D	0.491	neutral	None	None	None	None	N
T/D	0.7523	likely_pathogenic	0.779	pathogenic	-0.114	Destabilizing	0.346	N	0.463	neutral	None	None	None	None	N
T/E	0.6576	likely_pathogenic	0.6939	pathogenic	-0.141	Destabilizing	0.638	D	0.466	neutral	None	None	None	None	N
T/F	0.4995	ambiguous	0.5165	ambiguous	-0.825	Destabilizing	0.958	D	0.554	neutral	None	None	None	None	N
T/G	0.3203	likely_benign	0.331	benign	-0.896	Destabilizing	0.816	D	0.489	neutral	None	None	None	None	N
T/H	0.5409	ambiguous	0.5503	ambiguous	-1.177	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
T/I	0.2538	likely_benign	0.2493	benign	-0.165	Destabilizing	0.006	N	0.241	neutral	N	0.51980974	None	None	N
T/K	0.5684	likely_pathogenic	0.6125	pathogenic	-0.705	Destabilizing	0.711	D	0.461	neutral	None	None	None	None	N
T/L	0.144	likely_benign	0.15	benign	-0.165	Destabilizing	0.149	N	0.457	neutral	None	None	None	None	N
T/M	0.1226	likely_benign	0.1239	benign	0.079	Stabilizing	0.896	D	0.507	neutral	None	None	None	None	N
T/N	0.1953	likely_benign	0.1819	benign	-0.556	Destabilizing	0.285	N	0.369	neutral	N	0.512843696	None	None	N
T/P	0.1597	likely_benign	0.1382	benign	-0.301	Destabilizing	0.739	D	0.513	neutral	N	0.516596077	None	None	N
T/Q	0.4304	ambiguous	0.4365	ambiguous	-0.747	Destabilizing	0.891	D	0.518	neutral	None	None	None	None	N
T/R	0.485	ambiguous	0.5374	ambiguous	-0.427	Destabilizing	0.979	D	0.515	neutral	None	None	None	None	N
T/S	0.1409	likely_benign	0.1381	benign	-0.81	Destabilizing	0.002	N	0.138	neutral	N	0.488908043	None	None	N
T/V	0.1429	likely_benign	0.149	benign	-0.301	Destabilizing	0.111	N	0.359	neutral	None	None	None	None	N
T/W	0.8568	likely_pathogenic	0.8715	pathogenic	-0.773	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	N
T/Y	0.5604	ambiguous	0.5804	pathogenic	-0.544	Destabilizing	0.979	D	0.564	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.