TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1726	5401;5402;5403	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413
N2AB	1726	5401;5402;5403	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413
N2A	1726	5401;5402;5403	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413
N2B	1680	5263;5264;5265	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413
Novex-1	1680	5263;5264;5265	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413
Novex-2	1680	5263;5264;5265	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413
Novex-3	1726	5401;5402;5403	chr2:178776688;178776687;178776686	chr2:179641415;179641414;179641413

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-8
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1016
• 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/V	rs2092262370	None	0.999	N	0.55	0.362	0.294206760003	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/V	rs2092262370	None	0.999	N	0.55	0.362	0.294206760003	gnomAD-4.0.0	2.02974E-06	None	None	None	None	N	None	1.7466E-05	0	None	0	0	None	0	0	0	0	3.40252E-05

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	0.9644	likely_pathogenic	0.956	pathogenic	-2.693	Highly Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
L/C	0.9689	likely_pathogenic	0.9593	pathogenic	-1.792	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-2.913	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/E	0.997	likely_pathogenic	0.9959	pathogenic	-2.723	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/F	0.9387	likely_pathogenic	0.9277	pathogenic	-1.602	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/G	0.9962	likely_pathogenic	0.9953	pathogenic	-3.205	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/H	0.9952	likely_pathogenic	0.9935	pathogenic	-2.562	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/I	0.2838	likely_benign	0.2649	benign	-1.217	Destabilizing	0.999	D	0.543	neutral	N	0.48704223	None	None	N
L/K	0.9949	likely_pathogenic	0.9929	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/M	0.5232	ambiguous	0.4729	ambiguous	-1.031	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/N	0.9967	likely_pathogenic	0.9954	pathogenic	-2.291	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/P	0.9981	likely_pathogenic	0.9978	pathogenic	-1.69	Destabilizing	1.0	D	0.873	deleterious	D	0.536866685	None	None	N
L/Q	0.9882	likely_pathogenic	0.9838	pathogenic	-2.22	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.681599155	None	None	N
L/R	0.9917	likely_pathogenic	0.9892	pathogenic	-1.651	Destabilizing	1.0	D	0.879	deleterious	D	0.64346093	None	None	N
L/S	0.9957	likely_pathogenic	0.9945	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/T	0.9716	likely_pathogenic	0.9638	pathogenic	-2.656	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/V	0.3106	likely_benign	0.2868	benign	-1.69	Destabilizing	0.999	D	0.55	neutral	N	0.431140597	None	None	N
L/W	0.9946	likely_pathogenic	0.993	pathogenic	-1.984	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/Y	0.993	likely_pathogenic	0.9909	pathogenic	-1.752	Destabilizing	1.0	D	0.859	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.