TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28276	85051;85052;85053	chr2:178561306;178561305;178561304	chr2:179426033;179426032;179426031
N2AB	26635	80128;80129;80130	chr2:178561306;178561305;178561304	chr2:179426033;179426032;179426031
N2A	25708	77347;77348;77349	chr2:178561306;178561305;178561304	chr2:179426033;179426032;179426031
N2B	19211	57856;57857;57858	chr2:178561306;178561305;178561304	chr2:179426033;179426032;179426031
Novex-1	19336	58231;58232;58233	chr2:178561306;178561305;178561304	chr2:179426033;179426032;179426031
Novex-2	19403	58432;58433;58434	chr2:178561306;178561305;178561304	chr2:179426033;179426032;179426031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-94
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1042
• 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
P/L	None	None	1.0	D	0.916	0.692	0.729455935219	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	None	0	0	0	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
P/A	0.8402	likely_pathogenic	0.8786	pathogenic	-1.953	Destabilizing	1.0	D	0.857	deleterious	N	0.518464117	None	None	N
P/C	0.9848	likely_pathogenic	0.9902	pathogenic	-1.145	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.9988	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/E	0.9963	likely_pathogenic	0.9968	pathogenic	-2.532	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/F	0.9991	likely_pathogenic	0.9994	pathogenic	-1.475	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/G	0.9845	likely_pathogenic	0.9875	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/H	0.9944	likely_pathogenic	0.9961	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/I	0.9891	likely_pathogenic	0.9932	pathogenic	-0.945	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/K	0.9978	likely_pathogenic	0.9982	pathogenic	-1.731	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/L	0.9613	likely_pathogenic	0.9734	pathogenic	-0.945	Destabilizing	1.0	D	0.916	deleterious	D	0.542391269	None	None	N
P/M	0.9924	likely_pathogenic	0.9956	pathogenic	-0.534	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/N	0.9962	likely_pathogenic	0.9974	pathogenic	-1.591	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/Q	0.9922	likely_pathogenic	0.9939	pathogenic	-1.681	Destabilizing	1.0	D	0.882	deleterious	D	0.540544845	None	None	N
P/R	0.9932	likely_pathogenic	0.9936	pathogenic	-1.287	Destabilizing	1.0	D	0.909	deleterious	D	0.540291355	None	None	N
P/S	0.9603	likely_pathogenic	0.9748	pathogenic	-1.996	Destabilizing	1.0	D	0.891	deleterious	N	0.490560493	None	None	N
P/T	0.9584	likely_pathogenic	0.9746	pathogenic	-1.844	Destabilizing	1.0	D	0.893	deleterious	D	0.530073912	None	None	N
P/V	0.9697	likely_pathogenic	0.9792	pathogenic	-1.253	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.901	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/Y	0.999	likely_pathogenic	0.9993	pathogenic	-1.628	Destabilizing	1.0	D	0.907	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.