TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23080	69463;69464;69465	chr2:178577097;178577096;178577095	chr2:179441824;179441823;179441822
N2AB	21439	64540;64541;64542	chr2:178577097;178577096;178577095	chr2:179441824;179441823;179441822
N2A	20512	61759;61760;61761	chr2:178577097;178577096;178577095	chr2:179441824;179441823;179441822
N2B	14015	42268;42269;42270	chr2:178577097;178577096;178577095	chr2:179441824;179441823;179441822
Novex-1	14140	42643;42644;42645	chr2:178577097;178577096;178577095	chr2:179441824;179441823;179441822
Novex-2	14207	42844;42845;42846	chr2:178577097;178577096;178577095	chr2:179441824;179441823;179441822
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: Fn3-55
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1333
• 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	rs949990037	-1.414	0.025	N	0.194	0.26	0.280181792013	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/K	rs949990037	-1.414	0.025	N	0.194	0.26	0.280181792013	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	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	0.9835	likely_pathogenic	0.9822	pathogenic	-2.2	Highly Destabilizing	0.845	D	0.542	neutral	None	None	None	None	N
R/C	0.6319	likely_pathogenic	0.6327	pathogenic	-1.939	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
R/D	0.9991	likely_pathogenic	0.9988	pathogenic	-0.851	Destabilizing	0.975	D	0.773	deleterious	None	None	None	None	N
R/E	0.9807	likely_pathogenic	0.9751	pathogenic	-0.633	Destabilizing	0.845	D	0.455	neutral	None	None	None	None	N
R/F	0.9951	likely_pathogenic	0.9947	pathogenic	-1.415	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
R/G	0.9713	likely_pathogenic	0.9711	pathogenic	-2.54	Highly Destabilizing	0.892	D	0.683	prob.neutral	N	0.520823385	None	None	N
R/H	0.827	likely_pathogenic	0.7943	pathogenic	-2.23	Highly Destabilizing	0.987	D	0.613	neutral	None	None	None	None	N
R/I	0.9833	likely_pathogenic	0.9831	pathogenic	-1.203	Destabilizing	0.983	D	0.815	deleterious	D	0.527317845	None	None	N
R/K	0.5558	ambiguous	0.4809	ambiguous	-1.274	Destabilizing	0.025	N	0.194	neutral	N	0.513497056	None	None	N
R/L	0.9591	likely_pathogenic	0.9563	pathogenic	-1.203	Destabilizing	0.916	D	0.683	prob.neutral	None	None	None	None	N
R/M	0.95	likely_pathogenic	0.9474	pathogenic	-1.644	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
R/N	0.9964	likely_pathogenic	0.9954	pathogenic	-1.221	Destabilizing	0.975	D	0.577	neutral	None	None	None	None	N
R/P	0.9996	likely_pathogenic	0.9996	pathogenic	-1.526	Destabilizing	0.987	D	0.793	deleterious	None	None	None	None	N
R/Q	0.5431	ambiguous	0.5028	ambiguous	-1.162	Destabilizing	0.975	D	0.555	neutral	None	None	None	None	N
R/S	0.9949	likely_pathogenic	0.9944	pathogenic	-2.234	Highly Destabilizing	0.892	D	0.647	neutral	N	0.493752227	None	None	N
R/T	0.987	likely_pathogenic	0.9857	pathogenic	-1.803	Destabilizing	0.967	D	0.727	prob.delet.	N	0.511922615	None	None	N
R/V	0.9779	likely_pathogenic	0.9777	pathogenic	-1.526	Destabilizing	0.975	D	0.799	deleterious	None	None	None	None	N
R/W	0.9351	likely_pathogenic	0.9355	pathogenic	-0.832	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
R/Y	0.9785	likely_pathogenic	0.9769	pathogenic	-0.741	Destabilizing	0.996	D	0.805	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.