TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6487	19684;19685;19686	chr2:178728365;178728364;178728363	chr2:179593092;179593091;179593090
N2AB	6170	18733;18734;18735	chr2:178728365;178728364;178728363	chr2:179593092;179593091;179593090
N2A	5243	15952;15953;15954	chr2:178728365;178728364;178728363	chr2:179593092;179593091;179593090
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-49
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1514
• 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
L/I	None	None	0.999	N	0.544	0.21	0.283371740733	gnomAD-4.0.0	6.89078E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02773E-07	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
L/A	0.8764	likely_pathogenic	0.8929	pathogenic	-1.919	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
L/C	0.9533	likely_pathogenic	0.9612	pathogenic	-1.203	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/D	0.9962	likely_pathogenic	0.9945	pathogenic	-1.237	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/E	0.9796	likely_pathogenic	0.9734	pathogenic	-1.225	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/F	0.6395	likely_pathogenic	0.6392	pathogenic	-1.475	Destabilizing	1.0	D	0.747	deleterious	N	0.48643703	None	None	N
L/G	0.9773	likely_pathogenic	0.9767	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/H	0.9687	likely_pathogenic	0.9595	pathogenic	-1.462	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/I	0.1948	likely_benign	0.2181	benign	-1.012	Destabilizing	0.999	D	0.544	neutral	N	0.463368797	None	None	N
L/K	0.9728	likely_pathogenic	0.9619	pathogenic	-1.171	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/M	0.2205	likely_benign	0.2484	benign	-0.721	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
L/N	0.9718	likely_pathogenic	0.9683	pathogenic	-0.949	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/P	0.7873	likely_pathogenic	0.7617	pathogenic	-1.284	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/Q	0.922	likely_pathogenic	0.9069	pathogenic	-1.139	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/R	0.9581	likely_pathogenic	0.9398	pathogenic	-0.586	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/S	0.9766	likely_pathogenic	0.9773	pathogenic	-1.648	Destabilizing	1.0	D	0.858	deleterious	N	0.501009339	None	None	N
L/T	0.9091	likely_pathogenic	0.9171	pathogenic	-1.511	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/V	0.2689	likely_benign	0.3115	benign	-1.284	Destabilizing	0.999	D	0.529	neutral	N	0.497286356	None	None	N
L/W	0.9213	likely_pathogenic	0.894	pathogenic	-1.515	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/Y	0.9543	likely_pathogenic	0.9469	pathogenic	-1.303	Destabilizing	1.0	D	0.849	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.