TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28825	86698;86699;86700	chr2:178559659;178559658;178559657	chr2:179424386;179424385;179424384
N2AB	27184	81775;81776;81777	chr2:178559659;178559658;178559657	chr2:179424386;179424385;179424384
N2A	26257	78994;78995;78996	chr2:178559659;178559658;178559657	chr2:179424386;179424385;179424384
N2B	19760	59503;59504;59505	chr2:178559659;178559658;178559657	chr2:179424386;179424385;179424384
Novex-1	19885	59878;59879;59880	chr2:178559659;178559658;178559657	chr2:179424386;179424385;179424384
Novex-2	19952	60079;60080;60081	chr2:178559659;178559658;178559657	chr2:179424386;179424385;179424384
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-144
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0559
• 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/F	None	None	0.994	N	0.689	0.319	0.492816438443	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43583E-05	0
L/I	rs1575605256	None	0.248	N	0.387	0.05	0.171388866994	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43579E-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
L/A	0.7164	likely_pathogenic	0.6753	pathogenic	-2.375	Highly Destabilizing	0.97	D	0.744	deleterious	None	None	None	None	N
L/C	0.7511	likely_pathogenic	0.7451	pathogenic	-2.039	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.999	pathogenic	-2.389	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
L/E	0.9948	likely_pathogenic	0.9934	pathogenic	-2.139	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
L/F	0.6902	likely_pathogenic	0.654	pathogenic	-1.449	Destabilizing	0.994	D	0.689	prob.neutral	N	0.462617874	None	None	N
L/G	0.9689	likely_pathogenic	0.9599	pathogenic	-2.954	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/H	0.9894	likely_pathogenic	0.9864	pathogenic	-2.5	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/I	0.0891	likely_benign	0.0863	benign	-0.698	Destabilizing	0.248	N	0.387	neutral	N	0.46448124	None	None	N
L/K	0.9936	likely_pathogenic	0.9919	pathogenic	-1.696	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
L/M	0.2246	likely_benign	0.2024	benign	-0.906	Destabilizing	0.996	D	0.668	neutral	None	None	None	None	N
L/N	0.9939	likely_pathogenic	0.9915	pathogenic	-2.086	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
L/P	0.9943	likely_pathogenic	0.9931	pathogenic	-1.238	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
L/Q	0.9759	likely_pathogenic	0.9694	pathogenic	-1.879	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
L/R	0.9855	likely_pathogenic	0.9823	pathogenic	-1.592	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/S	0.9725	likely_pathogenic	0.9626	pathogenic	-2.877	Highly Destabilizing	0.994	D	0.813	deleterious	N	0.493599372	None	None	N
L/T	0.8671	likely_pathogenic	0.8466	pathogenic	-2.457	Highly Destabilizing	0.97	D	0.769	deleterious	None	None	None	None	N
L/V	0.0657	likely_benign	0.0665	benign	-1.238	Destabilizing	0.122	N	0.37	neutral	N	0.439814869	None	None	N
L/W	0.9797	likely_pathogenic	0.9736	pathogenic	-1.779	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/Y	0.976	likely_pathogenic	0.9703	pathogenic	-1.478	Destabilizing	0.999	D	0.757	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.