TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8583	25972;25973;25974	chr2:178715667;178715666;178715665	chr2:179580394;179580393;179580392
N2AB	8266	25021;25022;25023	chr2:178715667;178715666;178715665	chr2:179580394;179580393;179580392
N2A	7339	22240;22241;22242	chr2:178715667;178715666;178715665	chr2:179580394;179580393;179580392
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-71
• Domain position: 35
• Structural Position: 48
• Q(SASA): 0.1521
• 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
W/R	None	None	1.0	D	0.889	0.935	0.942336615409	gnomAD-4.0.0	2.05362E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69924E-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
W/A	0.9922	likely_pathogenic	0.9902	pathogenic	-3.022	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/C	0.9956	likely_pathogenic	0.9943	pathogenic	-1.666	Destabilizing	1.0	D	0.807	deleterious	D	0.718620484	None	None	N
W/D	0.9995	likely_pathogenic	0.9993	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
W/E	0.9992	likely_pathogenic	0.9991	pathogenic	-3.164	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
W/F	0.6996	likely_pathogenic	0.665	pathogenic	-1.774	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
W/G	0.9756	likely_pathogenic	0.9703	pathogenic	-3.254	Highly Destabilizing	1.0	D	0.804	deleterious	D	0.718418679	None	None	N
W/H	0.9957	likely_pathogenic	0.9948	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
W/I	0.9726	likely_pathogenic	0.9673	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
W/K	0.9996	likely_pathogenic	0.9995	pathogenic	-2.373	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
W/L	0.9105	likely_pathogenic	0.8978	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.804	deleterious	D	0.692880568	None	None	N
W/M	0.9886	likely_pathogenic	0.9855	pathogenic	-1.598	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
W/N	0.9991	likely_pathogenic	0.9988	pathogenic	-3.06	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
W/P	0.9979	likely_pathogenic	0.9973	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
W/Q	0.9993	likely_pathogenic	0.999	pathogenic	-2.918	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
W/R	0.9987	likely_pathogenic	0.9985	pathogenic	-2.068	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.718620484	None	None	N
W/S	0.9904	likely_pathogenic	0.9874	pathogenic	-3.217	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.718620484	None	None	N
W/T	0.9933	likely_pathogenic	0.9916	pathogenic	-3.04	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
W/V	0.9775	likely_pathogenic	0.9719	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/Y	0.9387	likely_pathogenic	0.931	pathogenic	-1.631	Destabilizing	1.0	D	0.814	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.