TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4007	12244;12245;12246	chr2:178741214;178741213;178741212	chr2:179605941;179605940;179605939
N2AB	3690	11293;11294;11295	chr2:178741214;178741213;178741212	chr2:179605941;179605940;179605939
N2A	None	None	chr2:None	chr2:None
N2B	3644	11155;11156;11157	chr2:178741214;178741213;178741212	chr2:179605941;179605940;179605939
Novex-1	3769	11530;11531;11532	chr2:178741214;178741213;178741212	chr2:179605941;179605940;179605939
Novex-2	3836	11731;11732;11733	chr2:178741214;178741213;178741212	chr2:179605941;179605940;179605939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-28
• Domain position: 70
• Structural Position: 152
• Q(SASA): 0.1445
• 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
G/D	rs940658679	-0.763	1.0	D	0.803	0.571	0.386721274199	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	0	1.40528E-04
G/D	rs940658679	-0.763	1.0	D	0.803	0.571	0.386721274199	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
G/D	rs940658679	-0.763	1.0	D	0.803	0.571	0.386721274199	gnomAD-4.0.0	2.56384E-06	None	None	None	None	N	None	0	3.39006E-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
G/A	0.4045	ambiguous	0.3929	ambiguous	-0.534	Destabilizing	1.0	D	0.719	prob.delet.	D	0.650458397	None	None	N
G/C	0.6903	likely_pathogenic	0.6374	pathogenic	-0.818	Destabilizing	1.0	D	0.757	deleterious	D	0.83535367	None	None	N
G/D	0.762	likely_pathogenic	0.763	pathogenic	-0.675	Destabilizing	1.0	D	0.803	deleterious	D	0.699191542	None	None	N
G/E	0.8438	likely_pathogenic	0.8349	pathogenic	-0.687	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/F	0.9487	likely_pathogenic	0.938	pathogenic	-0.741	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/H	0.929	likely_pathogenic	0.9134	pathogenic	-1.177	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/I	0.9264	likely_pathogenic	0.9139	pathogenic	0.002	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/K	0.9304	likely_pathogenic	0.9232	pathogenic	-1.037	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/L	0.9309	likely_pathogenic	0.914	pathogenic	0.002	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/M	0.9526	likely_pathogenic	0.9392	pathogenic	-0.103	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/N	0.8532	likely_pathogenic	0.8448	pathogenic	-0.799	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/P	0.9923	likely_pathogenic	0.992	pathogenic	-0.132	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/Q	0.8858	likely_pathogenic	0.8614	pathogenic	-0.865	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
G/R	0.8258	likely_pathogenic	0.804	pathogenic	-0.861	Destabilizing	1.0	D	0.815	deleterious	D	0.835302606	None	None	N
G/S	0.2967	likely_benign	0.2925	benign	-1.159	Destabilizing	1.0	D	0.805	deleterious	D	0.802503295	None	None	N
G/T	0.774	likely_pathogenic	0.7552	pathogenic	-1.063	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/V	0.8547	likely_pathogenic	0.8327	pathogenic	-0.132	Destabilizing	1.0	D	0.809	deleterious	D	0.83535367	None	None	N
G/W	0.9301	likely_pathogenic	0.9186	pathogenic	-1.176	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/Y	0.9324	likely_pathogenic	0.9209	pathogenic	-0.689	Destabilizing	1.0	D	0.77	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.