TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27738	83437;83438;83439	chr2:178562920;178562919;178562918	chr2:179427647;179427646;179427645
N2AB	26097	78514;78515;78516	chr2:178562920;178562919;178562918	chr2:179427647;179427646;179427645
N2A	25170	75733;75734;75735	chr2:178562920;178562919;178562918	chr2:179427647;179427646;179427645
N2B	18673	56242;56243;56244	chr2:178562920;178562919;178562918	chr2:179427647;179427646;179427645
Novex-1	18798	56617;56618;56619	chr2:178562920;178562919;178562918	chr2:179427647;179427646;179427645
Novex-2	18865	56818;56819;56820	chr2:178562920;178562919;178562918	chr2:179427647;179427646;179427645
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: Ig-141
• Domain position: 63
• Structural Position: 146
• Q(SASA): 0.7158
• Predicted PPI site: I

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	None	None	1.0	N	0.593	0.413	0.340753184043	gnomAD-4.0.0	6.84305E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99518E-07	0	0
R/K	None	None	0.997	N	0.546	0.362	0.298745278005	gnomAD-4.0.0	1.59179E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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	0.9837	likely_pathogenic	0.9872	pathogenic	-0.145	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	I
R/C	0.8825	likely_pathogenic	0.8875	pathogenic	-0.244	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
R/D	0.997	likely_pathogenic	0.9976	pathogenic	-0.023	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
R/E	0.9826	likely_pathogenic	0.9861	pathogenic	0.066	Stabilizing	0.999	D	0.646	neutral	None	None	None	None	I
R/F	0.9957	likely_pathogenic	0.9961	pathogenic	-0.312	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
R/G	0.981	likely_pathogenic	0.9836	pathogenic	-0.37	Destabilizing	1.0	D	0.593	neutral	N	0.508727886	None	None	I
R/H	0.7794	likely_pathogenic	0.7891	pathogenic	-1.008	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
R/I	0.9705	likely_pathogenic	0.9745	pathogenic	0.421	Stabilizing	1.0	D	0.733	prob.delet.	N	0.492318698	None	None	I
R/K	0.6745	likely_pathogenic	0.7014	pathogenic	-0.142	Destabilizing	0.997	D	0.546	neutral	N	0.459375417	None	None	I
R/L	0.9585	likely_pathogenic	0.9641	pathogenic	0.421	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	I
R/M	0.9865	likely_pathogenic	0.9886	pathogenic	-0.056	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
R/N	0.9923	likely_pathogenic	0.9937	pathogenic	0.068	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
R/P	0.9794	likely_pathogenic	0.9827	pathogenic	0.253	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
R/Q	0.7887	likely_pathogenic	0.7988	pathogenic	0.009	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
R/S	0.9901	likely_pathogenic	0.992	pathogenic	-0.337	Destabilizing	1.0	D	0.646	neutral	N	0.475366532	None	None	I
R/T	0.9878	likely_pathogenic	0.9904	pathogenic	-0.093	Destabilizing	1.0	D	0.641	neutral	N	0.473226938	None	None	I
R/V	0.9745	likely_pathogenic	0.9789	pathogenic	0.253	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
R/W	0.9402	likely_pathogenic	0.9378	pathogenic	-0.331	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
R/Y	0.9771	likely_pathogenic	0.9786	pathogenic	0.071	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I

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.