TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26029	78310;78311;78312	chr2:178568047;178568046;178568045	chr2:179432774;179432773;179432772
N2AB	24388	73387;73388;73389	chr2:178568047;178568046;178568045	chr2:179432774;179432773;179432772
N2A	23461	70606;70607;70608	chr2:178568047;178568046;178568045	chr2:179432774;179432773;179432772
N2B	16964	51115;51116;51117	chr2:178568047;178568046;178568045	chr2:179432774;179432773;179432772
Novex-1	17089	51490;51491;51492	chr2:178568047;178568046;178568045	chr2:179432774;179432773;179432772
Novex-2	17156	51691;51692;51693	chr2:178568047;178568046;178568045	chr2:179432774;179432773;179432772
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-77
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2116
• 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
R/K	None	None	0.002	N	0.389	0.054	0.180583059064	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.5979	likely_pathogenic	0.6666	pathogenic	-2.154	Highly Destabilizing	0.25	N	0.681	prob.neutral	None	None	None	None	N
R/C	0.1392	likely_benign	0.1564	benign	-2.04	Highly Destabilizing	0.982	D	0.753	deleterious	None	None	None	None	N
R/D	0.9601	likely_pathogenic	0.9703	pathogenic	-1.308	Destabilizing	0.7	D	0.733	prob.delet.	None	None	None	None	N
R/E	0.6538	likely_pathogenic	0.7026	pathogenic	-1.05	Destabilizing	0.25	N	0.671	neutral	None	None	None	None	N
R/F	0.592	likely_pathogenic	0.6249	pathogenic	-1.185	Destabilizing	0.935	D	0.781	deleterious	None	None	None	None	N
R/G	0.5348	ambiguous	0.6047	pathogenic	-2.544	Highly Destabilizing	0.334	N	0.721	prob.delet.	N	0.486750788	None	None	N
R/H	0.1824	likely_benign	0.1962	benign	-1.888	Destabilizing	0.826	D	0.727	prob.delet.	None	None	None	None	N
R/I	0.3266	likely_benign	0.3819	ambiguous	-1.002	Destabilizing	0.781	D	0.78	deleterious	N	0.512995624	None	None	N
R/K	0.1001	likely_benign	0.1005	benign	-1.138	Destabilizing	0.002	N	0.389	neutral	N	0.43388148	None	None	N
R/L	0.3727	ambiguous	0.4062	ambiguous	-1.002	Destabilizing	0.399	N	0.721	prob.delet.	None	None	None	None	N
R/M	0.2432	likely_benign	0.2697	benign	-1.476	Destabilizing	0.982	D	0.723	prob.delet.	None	None	None	None	N
R/N	0.8434	likely_pathogenic	0.8822	pathogenic	-1.624	Destabilizing	0.7	D	0.679	prob.neutral	None	None	None	None	N
R/P	0.9931	likely_pathogenic	0.9945	pathogenic	-1.377	Destabilizing	0.826	D	0.746	deleterious	None	None	None	None	N
R/Q	0.1166	likely_benign	0.1298	benign	-1.432	Destabilizing	0.539	D	0.687	prob.neutral	None	None	None	None	N
R/S	0.6668	likely_pathogenic	0.7345	pathogenic	-2.56	Highly Destabilizing	0.201	N	0.684	prob.neutral	N	0.514939851	None	None	N
R/T	0.4462	ambiguous	0.5254	ambiguous	-2.057	Highly Destabilizing	0.638	D	0.7	prob.neutral	N	0.478001376	None	None	N
R/V	0.3989	ambiguous	0.4596	ambiguous	-1.377	Destabilizing	0.7	D	0.771	deleterious	None	None	None	None	N
R/W	0.2559	likely_benign	0.2868	benign	-0.609	Destabilizing	0.982	D	0.697	prob.neutral	None	None	None	None	N
R/Y	0.4126	ambiguous	0.4451	ambiguous	-0.551	Destabilizing	0.826	D	0.759	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.