TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5906	17941;17942;17943	chr2:178730949;178730948;178730947	chr2:179595676;179595675;179595674
N2AB	5589	16990;16991;16992	chr2:178730949;178730948;178730947	chr2:179595676;179595675;179595674
N2A	4662	14209;14210;14211	chr2:178730949;178730948;178730947	chr2:179595676;179595675;179595674
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-42
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1693
• 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/F	rs1239818599	-1.215	0.997	N	0.819	0.473	0.832531937271	gnomAD-2.1.1	8.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.38E-05	None	0	8.99E-06	0
C/F	rs1239818599	-1.215	0.997	N	0.819	0.473	0.832531937271	gnomAD-4.0.0	2.74728E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70626E-06	1.1731E-05	0
C/S	None	None	0.99	N	0.759	0.567	0.677216412824	gnomAD-4.0.0	1.60327E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88191E-06	0	0
C/Y	rs1239818599	None	0.994	N	0.821	0.444	0.798155654027	gnomAD-4.0.0	6.86819E-07	None	None	None	None	N	None	3.0012E-05	0	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
C/A	0.4581	ambiguous	0.529	ambiguous	-1.768	Destabilizing	0.982	D	0.646	neutral	None	None	None	None	N
C/D	0.834	likely_pathogenic	0.8846	pathogenic	-0.214	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
C/E	0.9142	likely_pathogenic	0.9371	pathogenic	-0.076	Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
C/F	0.4667	ambiguous	0.4867	ambiguous	-1.088	Destabilizing	0.997	D	0.819	deleterious	N	0.483326153	None	None	N
C/G	0.21	likely_benign	0.2468	benign	-2.101	Highly Destabilizing	0.997	D	0.811	deleterious	N	0.490074103	None	None	N
C/H	0.7556	likely_pathogenic	0.7807	pathogenic	-2.024	Highly Destabilizing	0.323	N	0.65	neutral	None	None	None	None	N
C/I	0.7186	likely_pathogenic	0.7748	pathogenic	-0.899	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
C/K	0.895	likely_pathogenic	0.9114	pathogenic	-0.798	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
C/L	0.6957	likely_pathogenic	0.7501	pathogenic	-0.899	Destabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	N
C/M	0.8154	likely_pathogenic	0.8334	pathogenic	0.049	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
C/N	0.6936	likely_pathogenic	0.7526	pathogenic	-0.952	Destabilizing	0.996	D	0.845	deleterious	None	None	None	None	N
C/P	0.9939	likely_pathogenic	0.9963	pathogenic	-1.163	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
C/Q	0.7843	likely_pathogenic	0.8061	pathogenic	-0.743	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
C/R	0.608	likely_pathogenic	0.65	pathogenic	-0.807	Destabilizing	0.997	D	0.857	deleterious	D	0.526381501	None	None	N
C/S	0.2568	likely_benign	0.3135	benign	-1.508	Destabilizing	0.99	D	0.759	deleterious	N	0.45128631	None	None	N
C/T	0.4607	ambiguous	0.5219	ambiguous	-1.167	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
C/V	0.587	likely_pathogenic	0.6456	pathogenic	-1.163	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
C/W	0.8193	likely_pathogenic	0.8381	pathogenic	-1.093	Destabilizing	1.0	D	0.799	deleterious	N	0.495442927	None	None	N
C/Y	0.648	likely_pathogenic	0.6954	pathogenic	-1.068	Destabilizing	0.994	D	0.821	deleterious	N	0.490327592	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.