TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6905	20938;20939;20940	chr2:178725491;178725490;178725489	chr2:179590218;179590217;179590216
N2AB	6588	19987;19988;19989	chr2:178725491;178725490;178725489	chr2:179590218;179590217;179590216
N2A	5661	17206;17207;17208	chr2:178725491;178725490;178725489	chr2:179590218;179590217;179590216
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-53
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.256
• 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
F/L	rs781202077	-1.1	0.001	N	0.297	0.162	0.373357554552	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
F/L	rs781202077	-1.1	0.001	N	0.297	0.162	0.373357554552	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86007E-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
F/A	0.5183	ambiguous	0.5596	ambiguous	-2.207	Highly Destabilizing	0.388	N	0.653	neutral	None	None	None	None	N
F/C	0.3223	likely_benign	0.3717	ambiguous	-1.216	Destabilizing	0.975	D	0.672	neutral	N	0.495011627	None	None	N
F/D	0.8029	likely_pathogenic	0.8218	pathogenic	-1.11	Destabilizing	0.818	D	0.703	prob.neutral	None	None	None	None	N
F/E	0.8505	likely_pathogenic	0.861	pathogenic	-1.003	Destabilizing	0.69	D	0.697	prob.neutral	None	None	None	None	N
F/G	0.7906	likely_pathogenic	0.818	pathogenic	-2.567	Highly Destabilizing	0.818	D	0.695	prob.neutral	None	None	None	None	N
F/H	0.4263	ambiguous	0.4651	ambiguous	-0.875	Destabilizing	0.005	N	0.429	neutral	None	None	None	None	N
F/I	0.2856	likely_benign	0.2863	benign	-1.114	Destabilizing	0.193	N	0.559	neutral	D	0.523861271	None	None	N
F/K	0.8566	likely_pathogenic	0.8735	pathogenic	-1.293	Destabilizing	0.69	D	0.699	prob.neutral	None	None	None	None	N
F/L	0.8269	likely_pathogenic	0.8195	pathogenic	-1.114	Destabilizing	0.001	N	0.297	neutral	N	0.482730269	None	None	N
F/M	0.5451	ambiguous	0.5527	ambiguous	-0.839	Destabilizing	0.69	D	0.597	neutral	None	None	None	None	N
F/N	0.5865	likely_pathogenic	0.6117	pathogenic	-1.4	Destabilizing	0.69	D	0.703	prob.neutral	None	None	None	None	N
F/P	0.9823	likely_pathogenic	0.9834	pathogenic	-1.473	Destabilizing	0.932	D	0.695	prob.neutral	None	None	None	None	N
F/Q	0.7664	likely_pathogenic	0.8001	pathogenic	-1.452	Destabilizing	0.69	D	0.695	prob.neutral	None	None	None	None	N
F/R	0.7218	likely_pathogenic	0.757	pathogenic	-0.672	Destabilizing	0.69	D	0.701	prob.neutral	None	None	None	None	N
F/S	0.403	ambiguous	0.4275	ambiguous	-2.203	Highly Destabilizing	0.627	D	0.698	prob.neutral	D	0.532864756	None	None	N
F/T	0.4656	ambiguous	0.4779	ambiguous	-1.999	Destabilizing	0.818	D	0.699	prob.neutral	None	None	None	None	N
F/V	0.2456	likely_benign	0.2485	benign	-1.473	Destabilizing	0.193	N	0.571	neutral	N	0.513238845	None	None	N
F/W	0.4063	ambiguous	0.4301	ambiguous	-0.242	Destabilizing	0.944	D	0.596	neutral	None	None	None	None	N
F/Y	0.0954	likely_benign	0.1047	benign	-0.469	Destabilizing	0.001	N	0.263	neutral	N	0.457713637	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.