TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30403	91432;91433;91434	chr2:178551693;178551692;178551691	chr2:179416420;179416419;179416418
N2AB	28762	86509;86510;86511	chr2:178551693;178551692;178551691	chr2:179416420;179416419;179416418
N2A	27835	83728;83729;83730	chr2:178551693;178551692;178551691	chr2:179416420;179416419;179416418
N2B	21338	64237;64238;64239	chr2:178551693;178551692;178551691	chr2:179416420;179416419;179416418
Novex-1	21463	64612;64613;64614	chr2:178551693;178551692;178551691	chr2:179416420;179416419;179416418
Novex-2	21530	64813;64814;64815	chr2:178551693;178551692;178551691	chr2:179416420;179416419;179416418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-109
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.1015
• 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
N/K	rs760102226	-0.119	1.0	D	0.755	0.615	0.257292322809	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
N/K	rs760102226	-0.119	1.0	D	0.755	0.615	0.257292322809	gnomAD-4.0.0	1.59536E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86696E-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
N/A	0.9978	likely_pathogenic	0.9981	pathogenic	0.037	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
N/C	0.9804	likely_pathogenic	0.9807	pathogenic	-0.329	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
N/D	0.9868	likely_pathogenic	0.9887	pathogenic	-2.306	Highly Destabilizing	0.999	D	0.617	neutral	D	0.525982081	None	None	N
N/E	0.9988	likely_pathogenic	0.9989	pathogenic	-2.209	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
N/F	0.9994	likely_pathogenic	0.9995	pathogenic	-0.383	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
N/G	0.9924	likely_pathogenic	0.9924	pathogenic	-0.183	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
N/H	0.9871	likely_pathogenic	0.9892	pathogenic	-0.132	Destabilizing	1.0	D	0.776	deleterious	D	0.557217068	None	None	N
N/I	0.9934	likely_pathogenic	0.9943	pathogenic	0.545	Stabilizing	1.0	D	0.815	deleterious	D	0.557470558	None	None	N
N/K	0.9984	likely_pathogenic	0.9985	pathogenic	0.193	Stabilizing	1.0	D	0.755	deleterious	D	0.538098855	None	None	N
N/L	0.9898	likely_pathogenic	0.9896	pathogenic	0.545	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
N/M	0.9948	likely_pathogenic	0.9954	pathogenic	0.726	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
N/P	0.9991	likely_pathogenic	0.9991	pathogenic	0.403	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
N/Q	0.999	likely_pathogenic	0.9992	pathogenic	-0.961	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
N/R	0.9981	likely_pathogenic	0.9981	pathogenic	0.379	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
N/S	0.9378	likely_pathogenic	0.9405	pathogenic	-0.484	Destabilizing	0.999	D	0.602	neutral	N	0.508838878	None	None	N
N/T	0.9689	likely_pathogenic	0.9673	pathogenic	-0.267	Destabilizing	0.999	D	0.725	prob.delet.	N	0.511076922	None	None	N
N/V	0.9923	likely_pathogenic	0.9933	pathogenic	0.403	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.501	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
N/Y	0.9927	likely_pathogenic	0.9939	pathogenic	0.068	Stabilizing	1.0	D	0.821	deleterious	D	0.557217068	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.