TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18945	57058;57059;57060	chr2:178598877;178598876;178598875	chr2:179463604;179463603;179463602
N2AB	17304	52135;52136;52137	chr2:178598877;178598876;178598875	chr2:179463604;179463603;179463602
N2A	16377	49354;49355;49356	chr2:178598877;178598876;178598875	chr2:179463604;179463603;179463602
N2B	9880	29863;29864;29865	chr2:178598877;178598876;178598875	chr2:179463604;179463603;179463602
Novex-1	10005	30238;30239;30240	chr2:178598877;178598876;178598875	chr2:179463604;179463603;179463602
Novex-2	10072	30439;30440;30441	chr2:178598877;178598876;178598875	chr2:179463604;179463603;179463602
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-25
• Domain position: 62
• Structural Position: 88
• Q(SASA): 0.477
• Predicted PPI site: I

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
G/S	None	None	1.0	N	0.602	0.413	0.321393169273	gnomAD-4.0.0	1.59226E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43324E-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
G/A	0.5648	likely_pathogenic	0.4648	ambiguous	-0.453	Destabilizing	1.0	D	0.533	neutral	N	0.46431903	None	None	I
G/C	0.824	likely_pathogenic	0.7485	pathogenic	-0.785	Destabilizing	1.0	D	0.653	neutral	D	0.522636615	None	None	I
G/D	0.8641	likely_pathogenic	0.7628	pathogenic	-0.829	Destabilizing	1.0	D	0.539	neutral	N	0.443770399	None	None	I
G/E	0.8835	likely_pathogenic	0.7909	pathogenic	-0.969	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	I
G/F	0.9702	likely_pathogenic	0.9523	pathogenic	-1.057	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
G/H	0.9592	likely_pathogenic	0.9151	pathogenic	-0.934	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
G/I	0.9512	likely_pathogenic	0.9096	pathogenic	-0.424	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
G/K	0.9694	likely_pathogenic	0.9322	pathogenic	-1.093	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	I
G/L	0.9428	likely_pathogenic	0.9089	pathogenic	-0.424	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
G/M	0.9584	likely_pathogenic	0.927	pathogenic	-0.414	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
G/N	0.8833	likely_pathogenic	0.7745	pathogenic	-0.622	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	I
G/P	0.9754	likely_pathogenic	0.9521	pathogenic	-0.397	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	I
G/Q	0.9292	likely_pathogenic	0.8607	pathogenic	-0.897	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	I
G/R	0.9394	likely_pathogenic	0.8854	pathogenic	-0.672	Destabilizing	1.0	D	0.584	neutral	N	0.480133844	None	None	I
G/S	0.56	ambiguous	0.4032	ambiguous	-0.757	Destabilizing	1.0	D	0.602	neutral	N	0.458065061	None	None	I
G/T	0.8138	likely_pathogenic	0.6638	pathogenic	-0.832	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	I
G/V	0.8932	likely_pathogenic	0.8203	pathogenic	-0.397	Destabilizing	1.0	D	0.641	neutral	N	0.474805382	None	None	I
G/W	0.9439	likely_pathogenic	0.9101	pathogenic	-1.284	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
G/Y	0.9508	likely_pathogenic	0.9139	pathogenic	-0.924	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I

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.