TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19996	60211;60212;60213	chr2:178591833;178591832;178591831	chr2:179456560;179456559;179456558
N2AB	18355	55288;55289;55290	chr2:178591833;178591832;178591831	chr2:179456560;179456559;179456558
N2A	17428	52507;52508;52509	chr2:178591833;178591832;178591831	chr2:179456560;179456559;179456558
N2B	10931	33016;33017;33018	chr2:178591833;178591832;178591831	chr2:179456560;179456559;179456558
Novex-1	11056	33391;33392;33393	chr2:178591833;178591832;178591831	chr2:179456560;179456559;179456558
Novex-2	11123	33592;33593;33594	chr2:178591833;178591832;178591831	chr2:179456560;179456559;179456558
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-33
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1016
• 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
L/R	rs1553645358	None	1.0	D	0.871	0.729	0.874292223918	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
L/V	rs2050272980	None	0.999	N	0.592	0.309	0.499535901811	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs2050272980	None	0.999	N	0.592	0.309	0.499535901811	gnomAD-4.0.0	3.84589E-06	None	None	None	None	N	None	1.69182E-05	0	None	0	0	None	0	0	4.78849E-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
L/A	0.9814	likely_pathogenic	0.9797	pathogenic	-2.814	Highly Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
L/C	0.9762	likely_pathogenic	0.9731	pathogenic	-1.683	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9999	pathogenic	-3.493	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.9991	pathogenic	-3.175	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/F	0.8314	likely_pathogenic	0.8342	pathogenic	-1.729	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
L/G	0.998	likely_pathogenic	0.9982	pathogenic	-3.387	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/H	0.9975	likely_pathogenic	0.9981	pathogenic	-3.131	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/I	0.2619	likely_benign	0.21	benign	-1.069	Destabilizing	0.999	D	0.569	neutral	N	0.47789706	None	None	N
L/K	0.9975	likely_pathogenic	0.9982	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/M	0.5058	ambiguous	0.4718	ambiguous	-1.156	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/N	0.9991	likely_pathogenic	0.9993	pathogenic	-2.933	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/P	0.9986	likely_pathogenic	0.9988	pathogenic	-1.646	Destabilizing	1.0	D	0.906	deleterious	D	0.553208278	None	None	N
L/Q	0.9968	likely_pathogenic	0.9973	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.553208278	None	None	N
L/R	0.9947	likely_pathogenic	0.996	pathogenic	-2.273	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.553208278	None	None	N
L/S	0.9985	likely_pathogenic	0.9987	pathogenic	-3.36	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/T	0.9896	likely_pathogenic	0.99	pathogenic	-2.89	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/V	0.3723	ambiguous	0.2928	benign	-1.646	Destabilizing	0.999	D	0.592	neutral	N	0.4999359	None	None	N
L/W	0.9909	likely_pathogenic	0.9921	pathogenic	-2.095	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/Y	0.9931	likely_pathogenic	0.9939	pathogenic	-1.948	Destabilizing	1.0	D	0.795	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.