TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26064	78415;78416;78417	chr2:178567942;178567941;178567940	chr2:179432669;179432668;179432667
N2AB	24423	73492;73493;73494	chr2:178567942;178567941;178567940	chr2:179432669;179432668;179432667
N2A	23496	70711;70712;70713	chr2:178567942;178567941;178567940	chr2:179432669;179432668;179432667
N2B	16999	51220;51221;51222	chr2:178567942;178567941;178567940	chr2:179432669;179432668;179432667
Novex-1	17124	51595;51596;51597	chr2:178567942;178567941;178567940	chr2:179432669;179432668;179432667
Novex-2	17191	51796;51797;51798	chr2:178567942;178567941;178567940	chr2:179432669;179432668;179432667
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: 75
• Structural Position: 107
• Q(SASA): 0.115
• 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/G	rs767325298	-2.576	0.505	D	0.549	0.446	0.580120749226	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
R/K	None	None	0.003	N	0.338	0.281	0.329020015101	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	0.9551	likely_pathogenic	0.9722	pathogenic	-2.174	Highly Destabilizing	0.404	N	0.561	neutral	None	None	None	None	N
R/C	0.5021	ambiguous	0.5288	ambiguous	-1.905	Destabilizing	0.991	D	0.771	deleterious	None	None	None	None	N
R/D	0.9968	likely_pathogenic	0.9978	pathogenic	-1.136	Destabilizing	0.404	N	0.55	neutral	None	None	None	None	N
R/E	0.9526	likely_pathogenic	0.9669	pathogenic	-0.913	Destabilizing	0.004	N	0.502	neutral	None	None	None	None	N
R/F	0.9754	likely_pathogenic	0.9775	pathogenic	-1.312	Destabilizing	0.967	D	0.752	deleterious	None	None	None	None	N
R/G	0.959	likely_pathogenic	0.9732	pathogenic	-2.501	Highly Destabilizing	0.505	D	0.549	neutral	D	0.55332582	None	None	N
R/H	0.3856	ambiguous	0.3536	ambiguous	-2.275	Highly Destabilizing	0.906	D	0.58	neutral	None	None	None	None	N
R/I	0.8677	likely_pathogenic	0.9054	pathogenic	-1.21	Destabilizing	0.879	D	0.747	deleterious	D	0.526827774	None	None	N
R/K	0.1839	likely_benign	0.2129	benign	-1.247	Destabilizing	0.003	N	0.338	neutral	N	0.487666295	None	None	N
R/L	0.8542	likely_pathogenic	0.8835	pathogenic	-1.21	Destabilizing	0.575	D	0.565	neutral	None	None	None	None	N
R/M	0.8677	likely_pathogenic	0.9059	pathogenic	-1.702	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
R/N	0.984	likely_pathogenic	0.9885	pathogenic	-1.348	Destabilizing	0.575	D	0.518	neutral	None	None	None	None	N
R/P	0.9987	likely_pathogenic	0.9992	pathogenic	-1.523	Destabilizing	0.906	D	0.677	prob.neutral	None	None	None	None	N
R/Q	0.3797	ambiguous	0.416	ambiguous	-1.175	Destabilizing	0.404	N	0.584	neutral	None	None	None	None	N
R/S	0.9745	likely_pathogenic	0.9832	pathogenic	-2.218	Highly Destabilizing	0.338	N	0.522	neutral	D	0.531926201	None	None	N
R/T	0.9304	likely_pathogenic	0.9399	pathogenic	-1.789	Destabilizing	0.505	D	0.528	neutral	N	0.511290732	None	None	N
R/V	0.8956	likely_pathogenic	0.9245	pathogenic	-1.523	Destabilizing	0.826	D	0.655	neutral	None	None	None	None	N
R/W	0.8045	likely_pathogenic	0.8017	pathogenic	-0.842	Destabilizing	0.991	D	0.738	prob.delet.	None	None	None	None	N
R/Y	0.9385	likely_pathogenic	0.9399	pathogenic	-0.749	Destabilizing	0.967	D	0.713	prob.delet.	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.