TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14944	45055;45056;45057	chr2:178622753;178622752;178622751	chr2:179487480;179487479;179487478
N2AB	13303	40132;40133;40134	chr2:178622753;178622752;178622751	chr2:179487480;179487479;179487478
N2A	12376	37351;37352;37353	chr2:178622753;178622752;178622751	chr2:179487480;179487479;179487478
N2B	5879	17860;17861;17862	chr2:178622753;178622752;178622751	chr2:179487480;179487479;179487478
Novex-1	6004	18235;18236;18237	chr2:178622753;178622752;178622751	chr2:179487480;179487479;179487478
Novex-2	6071	18436;18437;18438	chr2:178622753;178622752;178622751	chr2:179487480;179487479;179487478
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-101
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1496
• 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
F/S	None	None	0.999	D	0.827	0.792	0.857761757952	gnomAD-4.0.0	1.37943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80824E-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
F/A	0.9927	likely_pathogenic	0.9915	pathogenic	-2.845	Highly Destabilizing	0.983	D	0.785	deleterious	None	None	None	None	N
F/C	0.9811	likely_pathogenic	0.9777	pathogenic	-1.441	Destabilizing	1.0	D	0.819	deleterious	D	0.764025738	None	None	N
F/D	0.9972	likely_pathogenic	0.997	pathogenic	-2.47	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/E	0.9976	likely_pathogenic	0.9974	pathogenic	-2.357	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/G	0.9961	likely_pathogenic	0.9954	pathogenic	-3.208	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
F/H	0.9913	likely_pathogenic	0.9915	pathogenic	-1.468	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
F/I	0.811	likely_pathogenic	0.7983	pathogenic	-1.693	Destabilizing	0.576	D	0.453	neutral	N	0.51558244	None	None	N
F/K	0.9982	likely_pathogenic	0.9982	pathogenic	-1.514	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/L	0.9921	likely_pathogenic	0.9907	pathogenic	-1.693	Destabilizing	0.9	D	0.617	neutral	D	0.660808825	None	None	N
F/M	0.9535	likely_pathogenic	0.9483	pathogenic	-1.294	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
F/N	0.9908	likely_pathogenic	0.9904	pathogenic	-1.622	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.998	pathogenic	-2.08	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
F/Q	0.9977	likely_pathogenic	0.9976	pathogenic	-1.773	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
F/R	0.9967	likely_pathogenic	0.9967	pathogenic	-0.781	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
F/S	0.9934	likely_pathogenic	0.9924	pathogenic	-2.35	Highly Destabilizing	0.999	D	0.827	deleterious	D	0.763607207	None	None	N
F/T	0.9932	likely_pathogenic	0.9921	pathogenic	-2.146	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
F/V	0.8855	likely_pathogenic	0.8712	pathogenic	-2.08	Highly Destabilizing	0.956	D	0.678	prob.neutral	D	0.596215487	None	None	N
F/W	0.9445	likely_pathogenic	0.9288	pathogenic	-0.622	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
F/Y	0.6372	likely_pathogenic	0.6422	pathogenic	-0.929	Destabilizing	0.996	D	0.631	neutral	D	0.763675543	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.