TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22120	66583;66584;66585	chr2:178582011;178582010;178582009	chr2:179446738;179446737;179446736
N2AB	20479	61660;61661;61662	chr2:178582011;178582010;178582009	chr2:179446738;179446737;179446736
N2A	19552	58879;58880;58881	chr2:178582011;178582010;178582009	chr2:179446738;179446737;179446736
N2B	13055	39388;39389;39390	chr2:178582011;178582010;178582009	chr2:179446738;179446737;179446736
Novex-1	13180	39763;39764;39765	chr2:178582011;178582010;178582009	chr2:179446738;179446737;179446736
Novex-2	13247	39964;39965;39966	chr2:178582011;178582010;178582009	chr2:179446738;179446737;179446736
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: Fn3-48
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1483
• 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/R	None	None	1.0	D	0.853	0.887	0.927402277902	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86026E-06	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	0.983	likely_pathogenic	0.9843	pathogenic	-2.562	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
L/C	0.9541	likely_pathogenic	0.9606	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9995	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/E	0.9973	likely_pathogenic	0.9975	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/F	0.8498	likely_pathogenic	0.8595	pathogenic	-1.776	Destabilizing	1.0	D	0.882	deleterious	D	0.650582033	None	None	N
L/G	0.9945	likely_pathogenic	0.9948	pathogenic	-3.022	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/H	0.9937	likely_pathogenic	0.9938	pathogenic	-2.301	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.667408611	None	None	N
L/I	0.447	ambiguous	0.5154	ambiguous	-1.275	Destabilizing	0.999	D	0.845	deleterious	D	0.614748314	None	None	N
L/K	0.9931	likely_pathogenic	0.9934	pathogenic	-1.962	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/M	0.5664	likely_pathogenic	0.6059	pathogenic	-1.164	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/N	0.9951	likely_pathogenic	0.9951	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/P	0.9966	likely_pathogenic	0.997	pathogenic	-1.681	Destabilizing	1.0	D	0.857	deleterious	D	0.667408611	None	None	N
L/Q	0.988	likely_pathogenic	0.9885	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/R	0.9882	likely_pathogenic	0.9888	pathogenic	-1.407	Destabilizing	1.0	D	0.853	deleterious	D	0.65138925	None	None	N
L/S	0.9966	likely_pathogenic	0.9969	pathogenic	-2.776	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/T	0.9832	likely_pathogenic	0.9851	pathogenic	-2.525	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/V	0.5817	likely_pathogenic	0.6389	pathogenic	-1.681	Destabilizing	0.999	D	0.853	deleterious	D	0.56610446	None	None	N
L/W	0.9857	likely_pathogenic	0.9862	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/Y	0.9865	likely_pathogenic	0.9876	pathogenic	-1.811	Destabilizing	1.0	D	0.826	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.