TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23055	69388;69389;69390	chr2:178577172;178577171;178577170	chr2:179441899;179441898;179441897
N2AB	21414	64465;64466;64467	chr2:178577172;178577171;178577170	chr2:179441899;179441898;179441897
N2A	20487	61684;61685;61686	chr2:178577172;178577171;178577170	chr2:179441899;179441898;179441897
N2B	13990	42193;42194;42195	chr2:178577172;178577171;178577170	chr2:179441899;179441898;179441897
Novex-1	14115	42568;42569;42570	chr2:178577172;178577171;178577170	chr2:179441899;179441898;179441897
Novex-2	14182	42769;42770;42771	chr2:178577172;178577171;178577170	chr2:179441899;179441898;179441897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-55
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.7411
• 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
E/A	rs2046618372	None	0.999	N	0.632	0.395	0.388812400583	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs2046618372	None	0.999	N	0.632	0.395	0.388812400583	gnomAD-4.0.0	6.57851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47106E-05	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
E/A	0.6677	likely_pathogenic	0.6211	pathogenic	-0.8	Destabilizing	0.999	D	0.632	neutral	N	0.510976826	None	None	N
E/C	0.9866	likely_pathogenic	0.9825	pathogenic	-0.209	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/D	0.3631	ambiguous	0.3783	ambiguous	-0.72	Destabilizing	0.999	D	0.505	neutral	N	0.433110689	None	None	N
E/F	0.9834	likely_pathogenic	0.9787	pathogenic	-0.546	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/G	0.5148	ambiguous	0.482	ambiguous	-1.075	Destabilizing	1.0	D	0.632	neutral	D	0.523559335	None	None	N
E/H	0.9249	likely_pathogenic	0.9194	pathogenic	-0.662	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/I	0.9362	likely_pathogenic	0.9206	pathogenic	-0.077	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/K	0.6635	likely_pathogenic	0.6431	pathogenic	-0.077	Destabilizing	0.999	D	0.6	neutral	N	0.467886064	None	None	N
E/L	0.9112	likely_pathogenic	0.8846	pathogenic	-0.077	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/M	0.9188	likely_pathogenic	0.8912	pathogenic	0.291	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
E/N	0.7441	likely_pathogenic	0.7178	pathogenic	-0.467	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/P	0.9908	likely_pathogenic	0.9904	pathogenic	-0.298	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/Q	0.4515	ambiguous	0.4171	ambiguous	-0.421	Destabilizing	1.0	D	0.633	neutral	N	0.473419473	None	None	N
E/R	0.7836	likely_pathogenic	0.7697	pathogenic	0.094	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/S	0.6717	likely_pathogenic	0.6237	pathogenic	-0.697	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
E/T	0.7289	likely_pathogenic	0.6793	pathogenic	-0.471	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/V	0.8209	likely_pathogenic	0.7842	pathogenic	-0.298	Destabilizing	1.0	D	0.655	neutral	N	0.495398068	None	None	N
E/W	0.9923	likely_pathogenic	0.9906	pathogenic	-0.311	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/Y	0.9677	likely_pathogenic	0.9627	pathogenic	-0.282	Destabilizing	1.0	D	0.626	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.