TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3896	11911;11912;11913	chr2:178741547;178741546;178741545	chr2:179606274;179606273;179606272
N2AB	3579	10960;10961;10962	chr2:178741547;178741546;178741545	chr2:179606274;179606273;179606272
N2A	None	None	chr2:None	chr2:None
N2B	3533	10822;10823;10824	chr2:178741547;178741546;178741545	chr2:179606274;179606273;179606272
Novex-1	3658	11197;11198;11199	chr2:178741547;178741546;178741545	chr2:179606274;179606273;179606272
Novex-2	3725	11398;11399;11400	chr2:178741547;178741546;178741545	chr2:179606274;179606273;179606272
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-27
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1402
• Predicted PPI site: I

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
N/S	rs1207560844	None	0.999	D	0.555	0.49	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
N/S	rs1207560844	None	0.999	D	0.555	0.49	None	gnomAD-4.0.0	2.47863E-06	None	None	None	None	I	None	0	1.667E-05	None	0	0	None	0	0	2.54272E-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
N/A	0.9167	likely_pathogenic	0.8958	pathogenic	-1.002	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
N/C	0.7692	likely_pathogenic	0.7702	pathogenic	-0.317	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
N/D	0.699	likely_pathogenic	0.6463	pathogenic	-1.428	Destabilizing	0.999	D	0.59	neutral	D	0.76427153	None	None	I
N/E	0.9788	likely_pathogenic	0.9724	pathogenic	-1.299	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
N/F	0.9886	likely_pathogenic	0.9868	pathogenic	-0.785	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/G	0.8393	likely_pathogenic	0.8045	pathogenic	-1.344	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	I
N/H	0.7386	likely_pathogenic	0.7215	pathogenic	-1.048	Destabilizing	1.0	D	0.738	prob.delet.	D	0.766670733	None	None	I
N/I	0.9263	likely_pathogenic	0.9147	pathogenic	-0.123	Destabilizing	1.0	D	0.699	prob.neutral	D	0.767405593	None	None	I
N/K	0.9663	likely_pathogenic	0.9629	pathogenic	-0.348	Destabilizing	1.0	D	0.735	prob.delet.	D	0.76576111	None	None	I
N/L	0.8611	likely_pathogenic	0.8533	pathogenic	-0.123	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/M	0.9352	likely_pathogenic	0.923	pathogenic	0.364	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
N/P	0.9768	likely_pathogenic	0.9755	pathogenic	-0.388	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/Q	0.9732	likely_pathogenic	0.9696	pathogenic	-1.124	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
N/R	0.9551	likely_pathogenic	0.9554	pathogenic	-0.326	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
N/S	0.2363	likely_benign	0.2154	benign	-1.101	Destabilizing	0.999	D	0.555	neutral	D	0.567967795	None	None	I
N/T	0.5989	likely_pathogenic	0.5202	ambiguous	-0.792	Destabilizing	0.999	D	0.701	prob.neutral	D	0.66317436	None	None	I
N/V	0.9099	likely_pathogenic	0.8898	pathogenic	-0.388	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/W	0.9952	likely_pathogenic	0.9956	pathogenic	-0.577	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
N/Y	0.8907	likely_pathogenic	0.8927	pathogenic	-0.307	Destabilizing	1.0	D	0.725	prob.delet.	D	0.766670733	None	None	I

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.