TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23303	70132;70133;70134	chr2:178576225;178576224;178576223	chr2:179440952;179440951;179440950
N2AB	21662	65209;65210;65211	chr2:178576225;178576224;178576223	chr2:179440952;179440951;179440950
N2A	20735	62428;62429;62430	chr2:178576225;178576224;178576223	chr2:179440952;179440951;179440950
N2B	14238	42937;42938;42939	chr2:178576225;178576224;178576223	chr2:179440952;179440951;179440950
Novex-1	14363	43312;43313;43314	chr2:178576225;178576224;178576223	chr2:179440952;179440951;179440950
Novex-2	14430	43513;43514;43515	chr2:178576225;178576224;178576223	chr2:179440952;179440951;179440950
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-57
• Domain position: 64
• Structural Position: 93
• Q(SASA): 0.0958
• 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/D	None	None	0.999	N	0.854	0.713	0.816208988277	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.43013E-04	0
V/L	None	None	0.948	N	0.563	0.24	0.565722134273	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
V/A	0.7386	likely_pathogenic	0.7037	pathogenic	-1.788	Destabilizing	0.994	D	0.666	neutral	N	0.478986697	None	None	N
V/C	0.933	likely_pathogenic	0.9199	pathogenic	-1.242	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/D	0.9928	likely_pathogenic	0.9919	pathogenic	-2.578	Highly Destabilizing	0.999	D	0.854	deleterious	N	0.505484743	None	None	N
V/E	0.9797	likely_pathogenic	0.9763	pathogenic	-2.314	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/F	0.8156	likely_pathogenic	0.7697	pathogenic	-1.043	Destabilizing	0.998	D	0.809	deleterious	N	0.499480354	None	None	N
V/G	0.9296	likely_pathogenic	0.9235	pathogenic	-2.354	Highly Destabilizing	0.999	D	0.86	deleterious	D	0.532743257	None	None	N
V/H	0.9908	likely_pathogenic	0.9885	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/I	0.1003	likely_benign	0.0937	benign	-0.188	Destabilizing	0.543	D	0.222	neutral	N	0.483331652	None	None	N
V/K	0.9779	likely_pathogenic	0.9742	pathogenic	-1.466	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/L	0.5511	ambiguous	0.4737	ambiguous	-0.188	Destabilizing	0.948	D	0.563	neutral	N	0.458315777	None	None	N
V/M	0.6057	likely_pathogenic	0.519	ambiguous	-0.251	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
V/N	0.9768	likely_pathogenic	0.9736	pathogenic	-1.907	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/P	0.9867	likely_pathogenic	0.9866	pathogenic	-0.695	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Q	0.9697	likely_pathogenic	0.9624	pathogenic	-1.667	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/R	0.9669	likely_pathogenic	0.9637	pathogenic	-1.509	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/S	0.9094	likely_pathogenic	0.8982	pathogenic	-2.48	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/T	0.8437	likely_pathogenic	0.8202	pathogenic	-2.058	Highly Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
V/W	0.996	likely_pathogenic	0.9947	pathogenic	-1.622	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9819	likely_pathogenic	0.9766	pathogenic	-1.155	Destabilizing	1.0	D	0.803	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.