TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1792	5599;5600;5601	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215
N2AB	1792	5599;5600;5601	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215
N2A	1792	5599;5600;5601	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215
N2B	1746	5461;5462;5463	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215
Novex-1	1746	5461;5462;5463	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215
Novex-2	1746	5461;5462;5463	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215
Novex-3	1792	5599;5600;5601	chr2:178776490;178776489;178776488	chr2:179641217;179641216;179641215

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-8
• Domain position: 90
• Structural Position: 174
• Q(SASA): 0.0946
• 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	None	None	1.0	D	0.902	0.937	0.93403665911	gnomAD-4.0.0	1.60571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85675E-06	0	0
L/R	None	None	1.0	D	0.921	0.842	0.923557122293	gnomAD-4.0.0	1.60571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85675E-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	0.9792	likely_pathogenic	0.9675	pathogenic	-2.941	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
L/C	0.969	likely_pathogenic	0.9585	pathogenic	-2.302	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9998	pathogenic	-3.317	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.9986	pathogenic	-3.013	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/F	0.7859	likely_pathogenic	0.7694	pathogenic	-1.815	Destabilizing	1.0	D	0.831	deleterious	D	0.782101842	None	None	N
L/G	0.9976	likely_pathogenic	0.9967	pathogenic	-3.571	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/H	0.9968	likely_pathogenic	0.996	pathogenic	-3.102	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.813246651	None	None	N
L/I	0.3365	likely_benign	0.2906	benign	-1.065	Destabilizing	0.999	D	0.583	neutral	D	0.591085076	None	None	N
L/K	0.9983	likely_pathogenic	0.9976	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/M	0.4296	ambiguous	0.3844	ambiguous	-1.113	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/N	0.9988	likely_pathogenic	0.9984	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/P	0.9995	likely_pathogenic	0.9993	pathogenic	-1.677	Destabilizing	1.0	D	0.902	deleterious	D	0.813246651	None	None	N
L/Q	0.9953	likely_pathogenic	0.9932	pathogenic	-2.586	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/R	0.9958	likely_pathogenic	0.9939	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.921	deleterious	D	0.813246651	None	None	N
L/S	0.9979	likely_pathogenic	0.9968	pathogenic	-3.603	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/T	0.9905	likely_pathogenic	0.9847	pathogenic	-3.126	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/V	0.3875	ambiguous	0.3106	benign	-1.677	Destabilizing	0.999	D	0.583	neutral	D	0.632431407	None	None	N
L/W	0.9885	likely_pathogenic	0.9868	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/Y	0.9865	likely_pathogenic	0.9854	pathogenic	-1.979	Destabilizing	1.0	D	0.891	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.