TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3886	11881;11882;11883	chr2:178741577;178741576;178741575	chr2:179606304;179606303;179606302
N2AB	3569	10930;10931;10932	chr2:178741577;178741576;178741575	chr2:179606304;179606303;179606302
N2A	None	None	chr2:None	chr2:None
N2B	3523	10792;10793;10794	chr2:178741577;178741576;178741575	chr2:179606304;179606303;179606302
Novex-1	3648	11167;11168;11169	chr2:178741577;178741576;178741575	chr2:179606304;179606303;179606302
Novex-2	3715	11368;11369;11370	chr2:178741577;178741576;178741575	chr2:179606304;179606303;179606302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-27
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1075
• 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
D/E	rs1300492136	0.622	0.027	D	0.611	0.527	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
D/E	rs1300492136	0.622	0.027	D	0.611	0.527	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
D/A	0.7541	likely_pathogenic	0.6909	pathogenic	2.01	Highly Stabilizing	0.117	N	0.736	prob.delet.	D	0.711650531	None	None	N
D/C	0.9351	likely_pathogenic	0.9051	pathogenic	1.424	Stabilizing	0.935	D	0.813	deleterious	None	None	None	None	N
D/E	0.6896	likely_pathogenic	0.6297	pathogenic	-0.203	Destabilizing	0.027	N	0.611	neutral	D	0.663240541	None	None	N
D/F	0.9294	likely_pathogenic	0.8937	pathogenic	2.424	Highly Stabilizing	0.235	N	0.81	deleterious	None	None	None	None	N
D/G	0.7239	likely_pathogenic	0.6649	pathogenic	1.534	Stabilizing	0.062	N	0.676	prob.neutral	D	0.782618466	None	None	N
D/H	0.7306	likely_pathogenic	0.6428	pathogenic	2.013	Highly Stabilizing	0.001	N	0.489	neutral	D	0.56628007	None	None	N
D/I	0.9208	likely_pathogenic	0.8783	pathogenic	3.267	Highly Stabilizing	0.38	N	0.829	deleterious	None	None	None	None	N
D/K	0.9095	likely_pathogenic	0.8804	pathogenic	1.358	Stabilizing	0.081	N	0.703	prob.neutral	None	None	None	None	N
D/L	0.9062	likely_pathogenic	0.8705	pathogenic	3.267	Highly Stabilizing	0.149	N	0.784	deleterious	None	None	None	None	N
D/M	0.9412	likely_pathogenic	0.9158	pathogenic	3.315	Highly Stabilizing	0.935	D	0.822	deleterious	None	None	None	None	N
D/N	0.3629	ambiguous	0.3178	benign	0.479	Stabilizing	None	N	0.327	neutral	D	0.615645611	None	None	N
D/P	0.9944	likely_pathogenic	0.9924	pathogenic	2.883	Highly Stabilizing	0.555	D	0.777	deleterious	None	None	None	None	N
D/Q	0.8912	likely_pathogenic	0.853	pathogenic	0.927	Stabilizing	0.38	N	0.7	prob.neutral	None	None	None	None	N
D/R	0.9276	likely_pathogenic	0.9062	pathogenic	0.978	Stabilizing	0.38	N	0.808	deleterious	None	None	None	None	N
D/S	0.6684	likely_pathogenic	0.5947	pathogenic	0.258	Stabilizing	0.081	N	0.621	neutral	None	None	None	None	N
D/T	0.8664	likely_pathogenic	0.8145	pathogenic	0.719	Stabilizing	0.081	N	0.703	prob.neutral	None	None	None	None	N
D/V	0.8005	likely_pathogenic	0.7261	pathogenic	2.883	Highly Stabilizing	0.117	N	0.804	deleterious	D	0.747288915	None	None	N
D/W	0.98	likely_pathogenic	0.9707	pathogenic	2.064	Highly Stabilizing	0.824	D	0.816	deleterious	None	None	None	None	N
D/Y	0.5648	likely_pathogenic	0.4706	ambiguous	2.671	Highly Stabilizing	None	N	0.534	neutral	D	0.643659131	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.