TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28305	85138;85139;85140	chr2:178561219;178561218;178561217	chr2:179425946;179425945;179425944
N2AB	26664	80215;80216;80217	chr2:178561219;178561218;178561217	chr2:179425946;179425945;179425944
N2A	25737	77434;77435;77436	chr2:178561219;178561218;178561217	chr2:179425946;179425945;179425944
N2B	19240	57943;57944;57945	chr2:178561219;178561218;178561217	chr2:179425946;179425945;179425944
Novex-1	19365	58318;58319;58320	chr2:178561219;178561218;178561217	chr2:179425946;179425945;179425944
Novex-2	19432	58519;58520;58521	chr2:178561219;178561218;178561217	chr2:179425946;179425945;179425944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-94
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.7343
• Predicted PPI site: I

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	0.999	N	0.612	0.445	0.544082543865	gnomAD-4.0.0	2.73733E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.63736E-05	0
T/S	None	None	0.992	N	0.392	0.255	0.244539031024	gnomAD-4.0.0	6.84332E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15934E-05	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	0.112	likely_benign	0.0976	benign	-0.253	Destabilizing	0.767	D	0.219	neutral	N	0.50362678	None	None	I
T/C	0.6169	likely_pathogenic	0.5665	pathogenic	-0.336	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	I
T/D	0.6703	likely_pathogenic	0.5891	pathogenic	0.233	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
T/E	0.6069	likely_pathogenic	0.5361	ambiguous	0.152	Stabilizing	1.0	D	0.583	neutral	None	None	None	None	I
T/F	0.5741	likely_pathogenic	0.4996	ambiguous	-0.872	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
T/G	0.2775	likely_benign	0.2583	benign	-0.34	Destabilizing	0.997	D	0.541	neutral	None	None	None	None	I
T/H	0.4438	ambiguous	0.3816	ambiguous	-0.523	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
T/I	0.4061	ambiguous	0.3421	ambiguous	-0.148	Destabilizing	0.999	D	0.612	neutral	N	0.507976594	None	None	I
T/K	0.415	ambiguous	0.343	ambiguous	-0.25	Destabilizing	1.0	D	0.574	neutral	None	None	None	None	I
T/L	0.2003	likely_benign	0.1751	benign	-0.148	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	I
T/M	0.172	likely_benign	0.1527	benign	-0.166	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
T/N	0.1986	likely_benign	0.1707	benign	-0.086	Destabilizing	1.0	D	0.565	neutral	D	0.523983409	None	None	I
T/P	0.5224	ambiguous	0.4654	ambiguous	-0.157	Destabilizing	0.999	D	0.607	neutral	N	0.473376112	None	None	I
T/Q	0.3479	ambiguous	0.3061	benign	-0.265	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
T/R	0.3373	likely_benign	0.2714	benign	0.016	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	I
T/S	0.1269	likely_benign	0.1151	benign	-0.273	Destabilizing	0.992	D	0.392	neutral	N	0.457640987	None	None	I
T/V	0.2562	likely_benign	0.2243	benign	-0.157	Destabilizing	0.997	D	0.441	neutral	None	None	None	None	I
T/W	0.8576	likely_pathogenic	0.8136	pathogenic	-0.939	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
T/Y	0.5734	likely_pathogenic	0.5014	ambiguous	-0.619	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I

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.