TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28919	86980;86981;86982	chr2:178559377;178559376;178559375	chr2:179424104;179424103;179424102
N2AB	27278	82057;82058;82059	chr2:178559377;178559376;178559375	chr2:179424104;179424103;179424102
N2A	26351	79276;79277;79278	chr2:178559377;178559376;178559375	chr2:179424104;179424103;179424102
N2B	19854	59785;59786;59787	chr2:178559377;178559376;178559375	chr2:179424104;179424103;179424102
Novex-1	19979	60160;60161;60162	chr2:178559377;178559376;178559375	chr2:179424104;179424103;179424102
Novex-2	20046	60361;60362;60363	chr2:178559377;178559376;178559375	chr2:179424104;179424103;179424102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-98
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0793
• 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
V/I	None	None	0.18	N	0.31	0.175	0.430808444494	gnomAD-4.0.0	1.59192E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85966E-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
V/A	0.8549	likely_pathogenic	0.8794	pathogenic	-2.422	Highly Destabilizing	0.994	D	0.648	neutral	D	0.546225244	None	None	N
V/C	0.9482	likely_pathogenic	0.9598	pathogenic	-1.838	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9991	pathogenic	-3.421	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.615553787	None	None	N
V/E	0.9962	likely_pathogenic	0.9967	pathogenic	-3.102	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/F	0.8358	likely_pathogenic	0.8543	pathogenic	-1.34	Destabilizing	0.999	D	0.817	deleterious	D	0.557746134	None	None	N
V/G	0.9487	likely_pathogenic	0.9593	pathogenic	-3.018	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.615553787	None	None	N
V/H	0.998	likely_pathogenic	0.9985	pathogenic	-2.895	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/I	0.0857	likely_benign	0.0885	benign	-0.675	Destabilizing	0.18	N	0.31	neutral	N	0.492178501	None	None	N
V/K	0.9966	likely_pathogenic	0.997	pathogenic	-1.964	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/L	0.5897	likely_pathogenic	0.6222	pathogenic	-0.675	Destabilizing	0.849	D	0.595	neutral	N	0.512708851	None	None	N
V/M	0.7063	likely_pathogenic	0.7347	pathogenic	-0.962	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
V/N	0.994	likely_pathogenic	0.9954	pathogenic	-2.644	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/P	0.9971	likely_pathogenic	0.9976	pathogenic	-1.241	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/Q	0.9941	likely_pathogenic	0.9951	pathogenic	-2.291	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/R	0.9933	likely_pathogenic	0.9939	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/S	0.9722	likely_pathogenic	0.979	pathogenic	-3.134	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.9252	likely_pathogenic	0.9394	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/W	0.998	likely_pathogenic	0.9983	pathogenic	-1.92	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/Y	0.9871	likely_pathogenic	0.9898	pathogenic	-1.623	Destabilizing	1.0	D	0.835	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.