TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3051	9376;9377;9378	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410
N2AB	3051	9376;9377;9378	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410
N2A	3051	9376;9377;9378	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410
N2B	3005	9238;9239;9240	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410
Novex-1	3005	9238;9239;9240	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410
Novex-2	3005	9238;9239;9240	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410
Novex-3	3051	9376;9377;9378	chr2:178768685;178768684;178768683	chr2:179633412;179633411;179633410

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-20
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.0744
• 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	None	None	0.999	D	0.558	0.398	0.544389754888	gnomAD-4.0.0	1.59075E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85659E-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	0.9809	likely_pathogenic	0.965	pathogenic	-2.731	Highly Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
L/C	0.9707	likely_pathogenic	0.9574	pathogenic	-1.769	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.367	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/E	0.9995	likely_pathogenic	0.9992	pathogenic	-3.038	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/F	0.9801	likely_pathogenic	0.9756	pathogenic	-1.695	Destabilizing	1.0	D	0.758	deleterious	D	0.640075121	None	None	N
L/G	0.9978	likely_pathogenic	0.9959	pathogenic	-3.352	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/H	0.9988	likely_pathogenic	0.9986	pathogenic	-3.092	Highly Destabilizing	1.0	D	0.777	deleterious	D	0.681425978	None	None	N
L/I	0.577	likely_pathogenic	0.5231	ambiguous	-0.861	Destabilizing	0.999	D	0.559	neutral	D	0.633582126	None	None	N
L/K	0.9987	likely_pathogenic	0.9985	pathogenic	-1.999	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/M	0.8048	likely_pathogenic	0.7724	pathogenic	-0.936	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/N	0.9992	likely_pathogenic	0.9988	pathogenic	-2.729	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/P	0.9995	likely_pathogenic	0.9993	pathogenic	-1.476	Destabilizing	1.0	D	0.784	deleterious	D	0.681425978	None	None	N
L/Q	0.9984	likely_pathogenic	0.9975	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/R	0.9966	likely_pathogenic	0.9957	pathogenic	-2.106	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.681425978	None	None	N
L/S	0.9986	likely_pathogenic	0.9975	pathogenic	-3.289	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/T	0.9931	likely_pathogenic	0.9882	pathogenic	-2.79	Highly Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
L/V	0.6099	likely_pathogenic	0.5248	ambiguous	-1.476	Destabilizing	0.999	D	0.558	neutral	D	0.662714747	None	None	N
L/W	0.9988	likely_pathogenic	0.9987	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/Y	0.9979	likely_pathogenic	0.9976	pathogenic	-1.878	Destabilizing	1.0	D	0.797	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.