TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4971	15136;15137;15138	chr2:178735535;178735534;178735533	chr2:179600262;179600261;179600260
N2AB	4654	14185;14186;14187	chr2:178735535;178735534;178735533	chr2:179600262;179600261;179600260
N2A	3727	11404;11405;11406	chr2:178735535;178735534;178735533	chr2:179600262;179600261;179600260
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-32
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1047
• 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
C/G	rs537312655	-2.55	0.012	D	0.724	0.121	0.507628581994	gnomAD-2.1.1	3.97851E-04	None	None	None	None	N	None	0	2.67035E-03	None	0	0	None	0	None	0	3.26E-05	2.11416E-03
C/G	rs537312655	-2.55	0.012	D	0.724	0.121	0.507628581994	gnomAD-3.1.2	4.13929E-04	None	None	None	None	N	None	0	3.99424E-03	0	0	0	None	0	0	2.94E-05	0	0
C/G	rs537312655	-2.55	0.012	D	0.724	0.121	0.507628581994	gnomAD-4.0.0	1.16669E-04	None	None	None	None	N	None	0	2.8678E-03	None	0	0	None	0	0	1.19448E-05	0	1.46294E-04

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
C/A	0.1217	likely_benign	0.1586	benign	-1.622	Destabilizing	0.007	N	0.393	neutral	None	None	None	None	N
C/D	0.4622	ambiguous	0.5403	ambiguous	0.255	Stabilizing	0.038	N	0.751	deleterious	None	None	None	None	N
C/E	0.6996	likely_pathogenic	0.7551	pathogenic	0.339	Stabilizing	0.038	N	0.747	deleterious	None	None	None	None	N
C/F	0.1804	likely_benign	0.1977	benign	-1.106	Destabilizing	0.295	N	0.752	deleterious	D	0.633461606	None	None	N
C/G	0.0873	likely_benign	0.0979	benign	-1.907	Destabilizing	0.012	N	0.724	prob.delet.	D	0.530789164	None	None	N
C/H	0.3531	ambiguous	0.3815	ambiguous	-1.89	Destabilizing	0.356	N	0.745	deleterious	None	None	None	None	N
C/I	0.2509	likely_benign	0.3192	benign	-0.904	Destabilizing	0.038	N	0.735	prob.delet.	None	None	None	None	N
C/K	0.6374	likely_pathogenic	0.6791	pathogenic	-0.468	Destabilizing	0.038	N	0.749	deleterious	None	None	None	None	N
C/L	0.2432	likely_benign	0.3002	benign	-0.904	Destabilizing	0.016	N	0.695	prob.neutral	None	None	None	None	N
C/M	0.3963	ambiguous	0.4753	ambiguous	-0.223	Destabilizing	0.356	N	0.733	prob.delet.	None	None	None	None	N
C/N	0.2317	likely_benign	0.2919	benign	-0.379	Destabilizing	0.038	N	0.751	deleterious	None	None	None	None	N
C/P	0.8569	likely_pathogenic	0.9146	pathogenic	-1.118	Destabilizing	0.072	N	0.763	deleterious	None	None	None	None	N
C/Q	0.5123	ambiguous	0.547	ambiguous	-0.318	Destabilizing	0.214	N	0.774	deleterious	None	None	None	None	N
C/R	0.3701	ambiguous	0.3756	ambiguous	-0.415	Destabilizing	0.171	N	0.773	deleterious	D	0.529001762	None	None	N
C/S	0.0611	likely_benign	0.071	benign	-0.987	Destabilizing	None	N	0.403	neutral	N	0.455137968	None	None	N
C/T	0.0988	likely_benign	0.1304	benign	-0.714	Destabilizing	None	N	0.413	neutral	None	None	None	None	N
C/V	0.2079	likely_benign	0.2574	benign	-1.118	Destabilizing	0.016	N	0.705	prob.neutral	None	None	None	None	N
C/W	0.4077	ambiguous	0.4597	ambiguous	-1.027	Destabilizing	0.828	D	0.713	prob.delet.	D	0.6056504	None	None	N
C/Y	0.2166	likely_benign	0.2451	benign	-0.996	Destabilizing	0.295	N	0.748	deleterious	D	0.576509501	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.