TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24638	74137;74138;74139	chr2:178572220;178572219;178572218	chr2:179436947;179436946;179436945
N2AB	22997	69214;69215;69216	chr2:178572220;178572219;178572218	chr2:179436947;179436946;179436945
N2A	22070	66433;66434;66435	chr2:178572220;178572219;178572218	chr2:179436947;179436946;179436945
N2B	15573	46942;46943;46944	chr2:178572220;178572219;178572218	chr2:179436947;179436946;179436945
Novex-1	15698	47317;47318;47319	chr2:178572220;178572219;178572218	chr2:179436947;179436946;179436945
Novex-2	15765	47518;47519;47520	chr2:178572220;178572219;178572218	chr2:179436947;179436946;179436945
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: Fn3-67
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4258
• 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/K	rs867655242	None	0.844	N	0.515	0.272	0.257786959452	gnomAD-4.0.0	1.3687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99573E-07	0	1.65695E-05

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	0.3247	likely_benign	0.2981	benign	-0.735	Destabilizing	0.854	D	0.6	neutral	N	0.502205414	None	None	N
E/C	0.9265	likely_pathogenic	0.9171	pathogenic	-0.231	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
E/D	0.2211	likely_benign	0.2184	benign	-0.659	Destabilizing	0.604	D	0.502	neutral	N	0.499991828	None	None	N
E/F	0.9239	likely_pathogenic	0.9102	pathogenic	-0.495	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/G	0.3067	likely_benign	0.2883	benign	-0.998	Destabilizing	0.986	D	0.671	neutral	N	0.470055793	None	None	N
E/H	0.7844	likely_pathogenic	0.7627	pathogenic	-0.542	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
E/I	0.5491	ambiguous	0.5142	ambiguous	-0.047	Destabilizing	0.979	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.433	ambiguous	0.4087	ambiguous	-0.143	Destabilizing	0.844	D	0.515	neutral	N	0.478211047	None	None	N
E/L	0.5557	ambiguous	0.52	ambiguous	-0.047	Destabilizing	0.959	D	0.7	prob.neutral	None	None	None	None	N
E/M	0.613	likely_pathogenic	0.5697	pathogenic	0.274	Stabilizing	0.99	D	0.722	prob.delet.	None	None	None	None	N
E/N	0.4472	ambiguous	0.4204	ambiguous	-0.503	Destabilizing	0.916	D	0.658	neutral	None	None	None	None	N
E/P	0.8951	likely_pathogenic	0.8834	pathogenic	-0.256	Destabilizing	0.956	D	0.746	deleterious	None	None	None	None	N
E/Q	0.2421	likely_benign	0.217	benign	-0.445	Destabilizing	0.885	D	0.595	neutral	N	0.497567599	None	None	N
E/R	0.6012	likely_pathogenic	0.5808	pathogenic	0.08	Stabilizing	0.094	N	0.331	neutral	None	None	None	None	N
E/S	0.387	ambiguous	0.3562	ambiguous	-0.718	Destabilizing	0.885	D	0.599	neutral	None	None	None	None	N
E/T	0.3702	ambiguous	0.3429	ambiguous	-0.505	Destabilizing	0.974	D	0.734	prob.delet.	None	None	None	None	N
E/V	0.3388	likely_benign	0.3104	benign	-0.256	Destabilizing	0.962	D	0.719	prob.delet.	N	0.496260877	None	None	N
E/W	0.9765	likely_pathogenic	0.972	pathogenic	-0.286	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/Y	0.8763	likely_pathogenic	0.8592	pathogenic	-0.255	Destabilizing	0.999	D	0.737	prob.delet.	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.