TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27144	81655;81656;81657	chr2:178564702;178564701;178564700	chr2:179429429;179429428;179429427
N2AB	25503	76732;76733;76734	chr2:178564702;178564701;178564700	chr2:179429429;179429428;179429427
N2A	24576	73951;73952;73953	chr2:178564702;178564701;178564700	chr2:179429429;179429428;179429427
N2B	18079	54460;54461;54462	chr2:178564702;178564701;178564700	chr2:179429429;179429428;179429427
Novex-1	18204	54835;54836;54837	chr2:178564702;178564701;178564700	chr2:179429429;179429428;179429427
Novex-2	18271	55036;55037;55038	chr2:178564702;178564701;178564700	chr2:179429429;179429428;179429427
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-85
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2919
• 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
E/G	rs794729512	None	1.0	D	0.755	0.561	0.63502316858	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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
E/A	0.3943	ambiguous	0.4046	ambiguous	-0.872	Destabilizing	0.999	D	0.695	prob.neutral	N	0.4985913	None	None	N
E/C	0.8787	likely_pathogenic	0.8933	pathogenic	-0.219	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/D	0.8037	likely_pathogenic	0.7927	pathogenic	-1.471	Destabilizing	0.999	D	0.588	neutral	N	0.496060086	None	None	N
E/F	0.9069	likely_pathogenic	0.9205	pathogenic	-0.472	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/G	0.6929	likely_pathogenic	0.6941	pathogenic	-1.323	Destabilizing	1.0	D	0.755	deleterious	D	0.535813768	None	None	N
E/H	0.8762	likely_pathogenic	0.8848	pathogenic	-0.505	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/I	0.6241	likely_pathogenic	0.6578	pathogenic	0.411	Stabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
E/K	0.7341	likely_pathogenic	0.7348	pathogenic	-0.842	Destabilizing	0.999	D	0.646	neutral	N	0.476586251	None	None	N
E/L	0.7387	likely_pathogenic	0.7661	pathogenic	0.411	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/M	0.6131	likely_pathogenic	0.6426	pathogenic	1.104	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/N	0.8166	likely_pathogenic	0.8169	pathogenic	-1.278	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/P	0.9981	likely_pathogenic	0.9981	pathogenic	0.001	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.2262	likely_benign	0.2423	benign	-0.911	Destabilizing	1.0	D	0.709	prob.delet.	N	0.488486756	None	None	N
E/R	0.8017	likely_pathogenic	0.8026	pathogenic	-0.821	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/S	0.5017	ambiguous	0.5039	ambiguous	-1.884	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
E/T	0.5219	ambiguous	0.5433	ambiguous	-1.451	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/V	0.4566	ambiguous	0.4957	ambiguous	0.001	Stabilizing	1.0	D	0.777	deleterious	N	0.476345989	None	None	N
E/W	0.9879	likely_pathogenic	0.9879	pathogenic	-0.575	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/Y	0.8965	likely_pathogenic	0.9071	pathogenic	-0.252	Destabilizing	1.0	D	0.807	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.