TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33689	101290;101291;101292	chr2:178535550;178535549;178535548	chr2:179400277;179400276;179400275
N2AB	32048	96367;96368;96369	chr2:178535550;178535549;178535548	chr2:179400277;179400276;179400275
N2A	31121	93586;93587;93588	chr2:178535550;178535549;178535548	chr2:179400277;179400276;179400275
N2B	24624	74095;74096;74097	chr2:178535550;178535549;178535548	chr2:179400277;179400276;179400275
Novex-1	24749	74470;74471;74472	chr2:178535550;178535549;178535548	chr2:179400277;179400276;179400275
Novex-2	24816	74671;74672;74673	chr2:178535550;178535549;178535548	chr2:179400277;179400276;179400275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-132
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1797
• 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
V/A	None	None	0.995	N	0.385	0.231	0.491928505054	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.4478	ambiguous	0.3463	ambiguous	-0.648	Destabilizing	0.995	D	0.385	neutral	N	0.488934181	None	None	N
V/C	0.8739	likely_pathogenic	0.8317	pathogenic	-0.649	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
V/D	0.87	likely_pathogenic	0.7712	pathogenic	-0.227	Destabilizing	1.0	D	0.767	deleterious	N	0.477012373	None	None	N
V/E	0.6544	likely_pathogenic	0.5278	ambiguous	-0.341	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
V/F	0.4422	ambiguous	0.354	ambiguous	-0.932	Destabilizing	0.999	D	0.598	neutral	N	0.470010934	None	None	N
V/G	0.6868	likely_pathogenic	0.555	ambiguous	-0.784	Destabilizing	1.0	D	0.762	deleterious	N	0.488115189	None	None	N
V/H	0.8964	likely_pathogenic	0.8364	pathogenic	-0.348	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/I	0.0881	likely_benign	0.0853	benign	-0.439	Destabilizing	0.171	N	0.118	neutral	N	0.484760512	None	None	N
V/K	0.7022	likely_pathogenic	0.5312	ambiguous	-0.315	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/L	0.4236	ambiguous	0.3563	ambiguous	-0.439	Destabilizing	0.761	D	0.455	neutral	N	0.475196879	None	None	N
V/M	0.2825	likely_benign	0.2547	benign	-0.291	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
V/N	0.7191	likely_pathogenic	0.6175	pathogenic	-0.061	Destabilizing	0.997	D	0.765	deleterious	None	None	None	None	N
V/P	0.8401	likely_pathogenic	0.7312	pathogenic	-0.474	Destabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
V/Q	0.6663	likely_pathogenic	0.542	ambiguous	-0.356	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
V/R	0.6338	likely_pathogenic	0.4576	ambiguous	0.194	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/S	0.5797	likely_pathogenic	0.4657	ambiguous	-0.494	Destabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
V/T	0.3532	ambiguous	0.3053	benign	-0.508	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	N
V/W	0.9694	likely_pathogenic	0.9477	pathogenic	-0.962	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/Y	0.8716	likely_pathogenic	0.8079	pathogenic	-0.64	Destabilizing	1.0	D	0.583	neutral	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.