TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32899	98920;98921;98922	chr2:178539240;178539239;178539238	chr2:179403967;179403966;179403965
N2AB	31258	93997;93998;93999	chr2:178539240;178539239;178539238	chr2:179403967;179403966;179403965
N2A	30331	91216;91217;91218	chr2:178539240;178539239;178539238	chr2:179403967;179403966;179403965
N2B	23834	71725;71726;71727	chr2:178539240;178539239;178539238	chr2:179403967;179403966;179403965
Novex-1	23959	72100;72101;72102	chr2:178539240;178539239;178539238	chr2:179403967;179403966;179403965
Novex-2	24026	72301;72302;72303	chr2:178539240;178539239;178539238	chr2:179403967;179403966;179403965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-128
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2769
• 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
P/T	rs199689531	None	1.0	N	0.689	0.401	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs199689531	None	1.0	N	0.689	0.401	None	gnomAD-4.0.0	1.9713E-05	None	None	None	None	N	None	7.23624E-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
P/A	0.1016	likely_benign	0.0868	benign	-1.402	Destabilizing	1.0	D	0.653	neutral	N	0.510723323	None	None	N
P/C	0.6836	likely_pathogenic	0.6498	pathogenic	-1.357	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
P/D	0.9147	likely_pathogenic	0.9191	pathogenic	-1.814	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
P/E	0.7063	likely_pathogenic	0.7058	pathogenic	-1.847	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
P/F	0.8209	likely_pathogenic	0.8132	pathogenic	-1.386	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
P/G	0.5231	ambiguous	0.5321	ambiguous	-1.654	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
P/H	0.6372	likely_pathogenic	0.6122	pathogenic	-1.117	Destabilizing	1.0	D	0.683	prob.neutral	N	0.485638379	None	None	N
P/I	0.6346	likely_pathogenic	0.6125	pathogenic	-0.817	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
P/K	0.6855	likely_pathogenic	0.69	pathogenic	-1.076	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
P/L	0.433	ambiguous	0.4178	ambiguous	-0.817	Destabilizing	1.0	D	0.704	prob.neutral	N	0.479255596	None	None	N
P/M	0.6132	likely_pathogenic	0.586	pathogenic	-0.708	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
P/N	0.7943	likely_pathogenic	0.7838	pathogenic	-0.984	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
P/Q	0.4597	ambiguous	0.4445	ambiguous	-1.28	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
P/R	0.5822	likely_pathogenic	0.5814	pathogenic	-0.528	Destabilizing	1.0	D	0.719	prob.delet.	N	0.476484119	None	None	N
P/S	0.3079	likely_benign	0.2821	benign	-1.437	Destabilizing	1.0	D	0.705	prob.neutral	N	0.479255596	None	None	N
P/T	0.3704	ambiguous	0.3473	ambiguous	-1.37	Destabilizing	1.0	D	0.689	prob.neutral	N	0.47597714	None	None	N
P/V	0.4808	ambiguous	0.4466	ambiguous	-0.979	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
P/W	0.9446	likely_pathogenic	0.9446	pathogenic	-1.489	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/Y	0.8277	likely_pathogenic	0.8214	pathogenic	-1.166	Destabilizing	1.0	D	0.696	prob.neutral	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.