TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32879	98860;98861;98862	chr2:178539430;178539429;178539428	chr2:179404157;179404156;179404155
N2AB	31238	93937;93938;93939	chr2:178539430;178539429;178539428	chr2:179404157;179404156;179404155
N2A	30311	91156;91157;91158	chr2:178539430;178539429;178539428	chr2:179404157;179404156;179404155
N2B	23814	71665;71666;71667	chr2:178539430;178539429;178539428	chr2:179404157;179404156;179404155
Novex-1	23939	72040;72041;72042	chr2:178539430;178539429;178539428	chr2:179404157;179404156;179404155
Novex-2	24006	72241;72242;72243	chr2:178539430;178539429;178539428	chr2:179404157;179404156;179404155
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-127
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1119
• 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
S/G	rs376395673	None	0.999	N	0.752	0.322	None	gnomAD-4.0.0	1.36842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79895E-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
S/A	0.4332	ambiguous	0.3827	ambiguous	-0.817	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
S/C	0.6331	likely_pathogenic	0.5402	ambiguous	-0.859	Destabilizing	1.0	D	0.831	deleterious	D	0.538804919	None	None	N
S/D	0.9883	likely_pathogenic	0.9813	pathogenic	-1.115	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
S/E	0.9947	likely_pathogenic	0.992	pathogenic	-1.104	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
S/F	0.9931	likely_pathogenic	0.9872	pathogenic	-1.088	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
S/G	0.1516	likely_benign	0.1321	benign	-1.042	Destabilizing	0.999	D	0.752	deleterious	N	0.462688942	None	None	N
S/H	0.9862	likely_pathogenic	0.9783	pathogenic	-1.5	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
S/I	0.994	likely_pathogenic	0.9892	pathogenic	-0.319	Destabilizing	1.0	D	0.907	deleterious	D	0.527702104	None	None	N
S/K	0.9991	likely_pathogenic	0.9984	pathogenic	-0.826	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
S/L	0.9581	likely_pathogenic	0.9253	pathogenic	-0.319	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/M	0.9818	likely_pathogenic	0.9698	pathogenic	-0.012	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
S/N	0.9418	likely_pathogenic	0.9143	pathogenic	-0.958	Destabilizing	0.999	D	0.748	deleterious	D	0.537790961	None	None	N
S/P	0.9906	likely_pathogenic	0.9833	pathogenic	-0.454	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
S/Q	0.9916	likely_pathogenic	0.9877	pathogenic	-1.207	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
S/R	0.9974	likely_pathogenic	0.9956	pathogenic	-0.632	Destabilizing	1.0	D	0.845	deleterious	D	0.526688146	None	None	N
S/T	0.6939	likely_pathogenic	0.6334	pathogenic	-0.893	Destabilizing	0.999	D	0.739	prob.delet.	D	0.538044451	None	None	N
S/V	0.9866	likely_pathogenic	0.977	pathogenic	-0.454	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
S/W	0.9928	likely_pathogenic	0.9869	pathogenic	-1.07	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
S/Y	0.9879	likely_pathogenic	0.9786	pathogenic	-0.773	Destabilizing	1.0	D	0.899	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.