TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27729	83410;83411;83412	chr2:178562947;178562946;178562945	chr2:179427674;179427673;179427672
N2AB	26088	78487;78488;78489	chr2:178562947;178562946;178562945	chr2:179427674;179427673;179427672
N2A	25161	75706;75707;75708	chr2:178562947;178562946;178562945	chr2:179427674;179427673;179427672
N2B	18664	56215;56216;56217	chr2:178562947;178562946;178562945	chr2:179427674;179427673;179427672
Novex-1	18789	56590;56591;56592	chr2:178562947;178562946;178562945	chr2:179427674;179427673;179427672
Novex-2	18856	56791;56792;56793	chr2:178562947;178562946;178562945	chr2:179427674;179427673;179427672
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-141
• Domain position: 54
• Structural Position: 136
• Q(SASA): 0.0952
• 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	rs753299607	0.58	0.988	N	0.755	0.456	0.410603549233	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
T/I	rs753299607	0.58	0.988	N	0.755	0.456	0.410603549233	gnomAD-4.0.0	1.59161E-06	None	None	None	None	N	None	0	0	None	0	2.77824E-05	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
T/A	0.4353	ambiguous	0.4592	ambiguous	-1.156	Destabilizing	0.067	N	0.502	neutral	N	0.484528439	None	None	N
T/C	0.8581	likely_pathogenic	0.8665	pathogenic	-0.776	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
T/D	0.9924	likely_pathogenic	0.9949	pathogenic	-2.28	Highly Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	N
T/E	0.995	likely_pathogenic	0.9963	pathogenic	-1.945	Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
T/F	0.9941	likely_pathogenic	0.995	pathogenic	-0.66	Destabilizing	0.995	D	0.826	deleterious	None	None	None	None	N
T/G	0.8617	likely_pathogenic	0.8712	pathogenic	-1.597	Destabilizing	0.938	D	0.713	prob.delet.	None	None	None	None	N
T/H	0.9829	likely_pathogenic	0.9863	pathogenic	-1.359	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
T/I	0.9776	likely_pathogenic	0.9804	pathogenic	0.083	Stabilizing	0.988	D	0.755	deleterious	N	0.477733162	None	None	N
T/K	0.9941	likely_pathogenic	0.9955	pathogenic	-0.073	Destabilizing	0.988	D	0.745	deleterious	N	0.47874712	None	None	N
T/L	0.8547	likely_pathogenic	0.8743	pathogenic	0.083	Stabilizing	0.938	D	0.665	neutral	None	None	None	None	N
T/M	0.7781	likely_pathogenic	0.809	pathogenic	-0.474	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/N	0.9263	likely_pathogenic	0.9465	pathogenic	-1.303	Destabilizing	0.995	D	0.735	prob.delet.	None	None	None	None	N
T/P	0.9685	likely_pathogenic	0.9784	pathogenic	-0.309	Destabilizing	0.994	D	0.789	deleterious	N	0.505245166	None	None	N
T/Q	0.9829	likely_pathogenic	0.9861	pathogenic	-0.752	Destabilizing	0.995	D	0.804	deleterious	None	None	None	None	N
T/R	0.9907	likely_pathogenic	0.9929	pathogenic	-0.708	Destabilizing	0.994	D	0.796	deleterious	N	0.468022698	None	None	N
T/S	0.3141	likely_benign	0.3059	benign	-1.449	Destabilizing	0.919	D	0.599	neutral	N	0.436062488	None	None	N
T/V	0.8768	likely_pathogenic	0.8836	pathogenic	-0.309	Destabilizing	0.938	D	0.609	neutral	None	None	None	None	N
T/W	0.9989	likely_pathogenic	0.9991	pathogenic	-0.916	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/Y	0.9949	likely_pathogenic	0.996	pathogenic	-0.547	Destabilizing	0.998	D	0.827	deleterious	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.