TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29670	89233;89234;89235	chr2:178554103;178554102;178554101	chr2:179418830;179418829;179418828
N2AB	28029	84310;84311;84312	chr2:178554103;178554102;178554101	chr2:179418830;179418829;179418828
N2A	27102	81529;81530;81531	chr2:178554103;178554102;178554101	chr2:179418830;179418829;179418828
N2B	20605	62038;62039;62040	chr2:178554103;178554102;178554101	chr2:179418830;179418829;179418828
Novex-1	20730	62413;62414;62415	chr2:178554103;178554102;178554101	chr2:179418830;179418829;179418828
Novex-2	20797	62614;62615;62616	chr2:178554103;178554102;178554101	chr2:179418830;179418829;179418828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-104
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0914
• 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/P	rs931707459	-2.45	1.0	N	0.897	0.726	0.833606934997	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/P	rs931707459	-2.45	1.0	N	0.897	0.726	0.833606934997	gnomAD-4.0.0	2.05256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-06	1.15937E-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	0.9042	likely_pathogenic	0.9205	pathogenic	-3.335	Highly Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
L/C	0.889	likely_pathogenic	0.9045	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.938	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/E	0.9973	likely_pathogenic	0.998	pathogenic	-3.632	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/F	0.8626	likely_pathogenic	0.883	pathogenic	-2.086	Highly Destabilizing	1.0	D	0.783	deleterious	D	0.526916679	None	None	N
L/G	0.9932	likely_pathogenic	0.9944	pathogenic	-3.881	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/H	0.9943	likely_pathogenic	0.9957	pathogenic	-3.346	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.527170169	None	None	N
L/I	0.1462	likely_benign	0.1617	benign	-1.654	Destabilizing	0.999	D	0.561	neutral	N	0.425757855	None	None	N
L/K	0.9961	likely_pathogenic	0.9967	pathogenic	-2.871	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/M	0.4109	ambiguous	0.4381	ambiguous	-1.706	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
L/N	0.9987	likely_pathogenic	0.9989	pathogenic	-3.635	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/P	0.9927	likely_pathogenic	0.9949	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.897	deleterious	N	0.504457558	None	None	N
L/Q	0.9883	likely_pathogenic	0.9909	pathogenic	-3.291	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/R	0.9896	likely_pathogenic	0.9922	pathogenic	-2.781	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.527170169	None	None	N
L/S	0.9914	likely_pathogenic	0.9937	pathogenic	-4.069	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/T	0.9155	likely_pathogenic	0.938	pathogenic	-3.618	Highly Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
L/V	0.1331	likely_benign	0.1465	benign	-2.213	Highly Destabilizing	0.999	D	0.587	neutral	N	0.400875266	None	None	N
L/W	0.9853	likely_pathogenic	0.9901	pathogenic	-2.317	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/Y	0.9913	likely_pathogenic	0.993	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.811	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.