TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26162	78709;78710;78711	chr2:178567648;178567647;178567646	chr2:179432375;179432374;179432373
N2AB	24521	73786;73787;73788	chr2:178567648;178567647;178567646	chr2:179432375;179432374;179432373
N2A	23594	71005;71006;71007	chr2:178567648;178567647;178567646	chr2:179432375;179432374;179432373
N2B	17097	51514;51515;51516	chr2:178567648;178567647;178567646	chr2:179432375;179432374;179432373
Novex-1	17222	51889;51890;51891	chr2:178567648;178567647;178567646	chr2:179432375;179432374;179432373
Novex-2	17289	52090;52091;52092	chr2:178567648;178567647;178567646	chr2:179432375;179432374;179432373
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: Fn3-78
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1311
• 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	rs145185269	-1.467	0.997	N	0.665	0.338	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
R/K	rs145185269	-1.467	0.997	N	0.665	0.338	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/K	rs145185269	-1.467	0.997	N	0.665	0.338	None	gnomAD-4.0.0	5.58176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.63426E-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	0.9877	likely_pathogenic	0.9878	pathogenic	-2.021	Highly Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
R/C	0.6557	likely_pathogenic	0.6104	pathogenic	-1.94	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
R/D	0.9985	likely_pathogenic	0.9985	pathogenic	-0.942	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
R/E	0.9791	likely_pathogenic	0.9773	pathogenic	-0.738	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
R/F	0.9876	likely_pathogenic	0.9865	pathogenic	-1.361	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
R/G	0.9845	likely_pathogenic	0.9855	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.739	prob.delet.	D	0.550931239	None	None	N
R/H	0.3129	likely_benign	0.2899	benign	-2.263	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
R/I	0.9801	likely_pathogenic	0.9744	pathogenic	-1.081	Destabilizing	1.0	D	0.851	deleterious	N	0.506974048	None	None	N
R/K	0.6495	likely_pathogenic	0.5603	ambiguous	-1.386	Destabilizing	0.997	D	0.665	neutral	N	0.493033622	None	None	N
R/L	0.9551	likely_pathogenic	0.9497	pathogenic	-1.081	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/M	0.9798	likely_pathogenic	0.974	pathogenic	-1.567	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
R/N	0.9905	likely_pathogenic	0.9898	pathogenic	-1.264	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
R/P	0.9995	likely_pathogenic	0.9995	pathogenic	-1.384	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
R/Q	0.5655	likely_pathogenic	0.4972	ambiguous	-1.179	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
R/S	0.9882	likely_pathogenic	0.9881	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.725	prob.delet.	N	0.514669823	None	None	N
R/T	0.9844	likely_pathogenic	0.9825	pathogenic	-1.766	Destabilizing	1.0	D	0.731	prob.delet.	N	0.493932221	None	None	N
R/V	0.9812	likely_pathogenic	0.9776	pathogenic	-1.384	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
R/W	0.8308	likely_pathogenic	0.8132	pathogenic	-0.893	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
R/Y	0.9488	likely_pathogenic	0.9447	pathogenic	-0.728	Destabilizing	1.0	D	0.846	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.