TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30485	91678;91679;91680	chr2:178551078;178551077;178551076	chr2:179415805;179415804;179415803
N2AB	28844	86755;86756;86757	chr2:178551078;178551077;178551076	chr2:179415805;179415804;179415803
N2A	27917	83974;83975;83976	chr2:178551078;178551077;178551076	chr2:179415805;179415804;179415803
N2B	21420	64483;64484;64485	chr2:178551078;178551077;178551076	chr2:179415805;179415804;179415803
Novex-1	21545	64858;64859;64860	chr2:178551078;178551077;178551076	chr2:179415805;179415804;179415803
Novex-2	21612	65059;65060;65061	chr2:178551078;178551077;178551076	chr2:179415805;179415804;179415803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-110
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.5085
• 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/R	rs748001852	-0.101	1.0	N	0.767	0.44	0.637519714765	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
G/R	rs748001852	-0.101	1.0	N	0.767	0.44	0.637519714765	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85961E-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
G/A	0.2152	likely_benign	0.2573	benign	-0.211	Destabilizing	0.974	D	0.479	neutral	N	0.475948504	None	None	N
G/C	0.4534	ambiguous	0.5364	ambiguous	-0.811	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/D	0.5437	ambiguous	0.6738	pathogenic	-0.488	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/E	0.6121	likely_pathogenic	0.743	pathogenic	-0.638	Destabilizing	1.0	D	0.753	deleterious	N	0.481099837	None	None	N
G/F	0.8539	likely_pathogenic	0.9093	pathogenic	-0.906	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/H	0.7157	likely_pathogenic	0.7977	pathogenic	-0.461	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/I	0.7648	likely_pathogenic	0.8487	pathogenic	-0.309	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/K	0.854	likely_pathogenic	0.9159	pathogenic	-0.77	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/L	0.7246	likely_pathogenic	0.8044	pathogenic	-0.309	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/M	0.735	likely_pathogenic	0.8103	pathogenic	-0.452	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
G/N	0.391	ambiguous	0.4785	ambiguous	-0.39	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
G/P	0.9676	likely_pathogenic	0.9825	pathogenic	-0.243	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
G/Q	0.6532	likely_pathogenic	0.7432	pathogenic	-0.649	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/R	0.7377	likely_pathogenic	0.8342	pathogenic	-0.352	Destabilizing	1.0	D	0.767	deleterious	N	0.477024914	None	None	N
G/S	0.1456	likely_benign	0.1727	benign	-0.546	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
G/T	0.38	ambiguous	0.4672	ambiguous	-0.622	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/V	0.6044	likely_pathogenic	0.7224	pathogenic	-0.243	Destabilizing	1.0	D	0.762	deleterious	D	0.537440519	None	None	N
G/W	0.8233	likely_pathogenic	0.8923	pathogenic	-1.086	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
G/Y	0.7778	likely_pathogenic	0.8538	pathogenic	-0.718	Destabilizing	1.0	D	0.783	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.