TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20719	62380;62381;62382	chr2:178589570;178589569;178589568	chr2:179454297;179454296;179454295
N2AB	19078	57457;57458;57459	chr2:178589570;178589569;178589568	chr2:179454297;179454296;179454295
N2A	18151	54676;54677;54678	chr2:178589570;178589569;178589568	chr2:179454297;179454296;179454295
N2B	11654	35185;35186;35187	chr2:178589570;178589569;178589568	chr2:179454297;179454296;179454295
Novex-1	11779	35560;35561;35562	chr2:178589570;178589569;178589568	chr2:179454297;179454296;179454295
Novex-2	11846	35761;35762;35763	chr2:178589570;178589569;178589568	chr2:179454297;179454296;179454295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-38
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.0981
• 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
H/P	rs1477967306	-1.023	0.998	N	0.537	0.373	0.368183359018	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.18203E-03	None	0	0	None	0	None	0	0	0
H/P	rs1477967306	-1.023	0.998	N	0.537	0.373	0.368183359018	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
H/P	rs1477967306	-1.023	0.998	N	0.537	0.373	0.368183359018	gnomAD-4.0.0	6.5786E-06	None	None	None	None	N	None	0	6.5548E-05	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
H/A	0.8392	likely_pathogenic	0.7907	pathogenic	-1.378	Destabilizing	0.864	D	0.526	neutral	None	None	None	None	N
H/C	0.4856	ambiguous	0.5355	ambiguous	-0.516	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	N
H/D	0.7996	likely_pathogenic	0.7829	pathogenic	-1.487	Destabilizing	0.921	D	0.511	neutral	N	0.475650744	None	None	N
H/E	0.9022	likely_pathogenic	0.8761	pathogenic	-1.315	Destabilizing	0.969	D	0.559	neutral	None	None	None	None	N
H/F	0.7075	likely_pathogenic	0.6953	pathogenic	0.403	Stabilizing	0.999	D	0.571	neutral	None	None	None	None	N
H/G	0.8129	likely_pathogenic	0.7903	pathogenic	-1.801	Destabilizing	0.927	D	0.531	neutral	None	None	None	None	N
H/I	0.8907	likely_pathogenic	0.865	pathogenic	-0.152	Destabilizing	0.995	D	0.583	neutral	None	None	None	None	N
H/K	0.9236	likely_pathogenic	0.873	pathogenic	-0.91	Destabilizing	0.969	D	0.515	neutral	None	None	None	None	N
H/L	0.6204	likely_pathogenic	0.5783	pathogenic	-0.152	Destabilizing	0.979	D	0.549	neutral	N	0.490081479	None	None	N
H/M	0.8836	likely_pathogenic	0.865	pathogenic	-0.349	Destabilizing	1.0	D	0.522	neutral	None	None	None	None	N
H/N	0.3578	ambiguous	0.364	ambiguous	-1.486	Destabilizing	0.116	N	0.188	neutral	N	0.397688606	None	None	N
H/P	0.7771	likely_pathogenic	0.7431	pathogenic	-0.547	Destabilizing	0.998	D	0.537	neutral	N	0.490428196	None	None	N
H/Q	0.7847	likely_pathogenic	0.7385	pathogenic	-1.142	Destabilizing	0.994	D	0.608	neutral	N	0.472214477	None	None	N
H/R	0.8163	likely_pathogenic	0.7425	pathogenic	-1.328	Destabilizing	0.979	D	0.603	neutral	N	0.5002584	None	None	N
H/S	0.6058	likely_pathogenic	0.5468	ambiguous	-1.48	Destabilizing	0.546	D	0.349	neutral	None	None	None	None	N
H/T	0.7741	likely_pathogenic	0.759	pathogenic	-1.189	Destabilizing	0.969	D	0.533	neutral	None	None	None	None	N
H/V	0.8353	likely_pathogenic	0.7979	pathogenic	-0.547	Destabilizing	0.995	D	0.557	neutral	None	None	None	None	N
H/W	0.7713	likely_pathogenic	0.7772	pathogenic	0.924	Stabilizing	1.0	D	0.562	neutral	None	None	None	None	N
H/Y	0.4005	ambiguous	0.4234	ambiguous	0.779	Stabilizing	0.998	D	0.583	neutral	N	0.482963506	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.