TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27410	82453;82454;82455	chr2:178563904;178563903;178563902	chr2:179428631;179428630;179428629
N2AB	25769	77530;77531;77532	chr2:178563904;178563903;178563902	chr2:179428631;179428630;179428629
N2A	24842	74749;74750;74751	chr2:178563904;178563903;178563902	chr2:179428631;179428630;179428629
N2B	18345	55258;55259;55260	chr2:178563904;178563903;178563902	chr2:179428631;179428630;179428629
Novex-1	18470	55633;55634;55635	chr2:178563904;178563903;178563902	chr2:179428631;179428630;179428629
Novex-2	18537	55834;55835;55836	chr2:178563904;178563903;178563902	chr2:179428631;179428630;179428629
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-87
• Domain position: 42
• Structural Position: 43
• Q(SASA): 0.1439
• 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	0.025	N	0.198	0.212	0.229924730088	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.9851	likely_pathogenic	0.9816	pathogenic	-2.312	Highly Destabilizing	0.845	D	0.532	neutral	None	None	None	None	N
R/C	0.6837	likely_pathogenic	0.6636	pathogenic	-2.056	Highly Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
R/D	0.9985	likely_pathogenic	0.9982	pathogenic	-0.902	Destabilizing	0.975	D	0.754	deleterious	None	None	None	None	N
R/E	0.9755	likely_pathogenic	0.9687	pathogenic	-0.693	Destabilizing	0.845	D	0.451	neutral	None	None	None	None	N
R/F	0.9956	likely_pathogenic	0.9941	pathogenic	-1.581	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
R/G	0.9696	likely_pathogenic	0.9628	pathogenic	-2.634	Highly Destabilizing	0.892	D	0.662	neutral	N	0.502389962	None	None	N
R/H	0.8131	likely_pathogenic	0.7821	pathogenic	-2.403	Highly Destabilizing	0.987	D	0.611	neutral	None	None	None	None	N
R/I	0.9847	likely_pathogenic	0.9809	pathogenic	-1.37	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
R/K	0.5222	ambiguous	0.4919	ambiguous	-1.402	Destabilizing	0.025	N	0.198	neutral	N	0.497066167	None	None	N
R/L	0.9604	likely_pathogenic	0.9557	pathogenic	-1.37	Destabilizing	0.916	D	0.662	neutral	None	None	None	None	N
R/M	0.9556	likely_pathogenic	0.9475	pathogenic	-1.814	Destabilizing	0.999	D	0.715	prob.delet.	N	0.480273236	None	None	N
R/N	0.9947	likely_pathogenic	0.9935	pathogenic	-1.267	Destabilizing	0.975	D	0.569	neutral	None	None	None	None	N
R/P	0.9995	likely_pathogenic	0.9993	pathogenic	-1.676	Destabilizing	0.987	D	0.778	deleterious	None	None	None	None	N
R/Q	0.5855	likely_pathogenic	0.5348	ambiguous	-1.226	Destabilizing	0.975	D	0.554	neutral	None	None	None	None	N
R/S	0.9949	likely_pathogenic	0.993	pathogenic	-2.284	Highly Destabilizing	0.892	D	0.617	neutral	N	0.482395922	None	None	N
R/T	0.9872	likely_pathogenic	0.9844	pathogenic	-1.869	Destabilizing	0.967	D	0.701	prob.neutral	N	0.496287122	None	None	N
R/V	0.9827	likely_pathogenic	0.9787	pathogenic	-1.676	Destabilizing	0.975	D	0.797	deleterious	None	None	None	None	N
R/W	0.9334	likely_pathogenic	0.9192	pathogenic	-1.006	Destabilizing	0.999	D	0.728	prob.delet.	N	0.498248905	None	None	N
R/Y	0.9774	likely_pathogenic	0.974	pathogenic	-0.918	Destabilizing	0.996	D	0.796	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.