TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7965	24118;24119;24120	chr2:178719599;178719598;178719597	chr2:179584326;179584325;179584324
N2AB	7648	23167;23168;23169	chr2:178719599;178719598;178719597	chr2:179584326;179584325;179584324
N2A	6721	20386;20387;20388	chr2:178719599;178719598;178719597	chr2:179584326;179584325;179584324
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-64
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1684
• 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
N/D	None	None	0.999	D	0.603	0.589	0.407357902709	gnomAD-4.0.0	3.42398E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.50175E-06	0	0
N/K	rs1363515138	None	1.0	D	0.733	0.483	0.240491677333	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
N/K	rs1363515138	None	1.0	D	0.733	0.483	0.240491677333	gnomAD-4.0.0	1.3146E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94048E-05	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	0.9951	likely_pathogenic	0.9954	pathogenic	-0.777	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
N/C	0.9829	likely_pathogenic	0.9854	pathogenic	-0.202	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
N/D	0.9606	likely_pathogenic	0.9703	pathogenic	-1.214	Destabilizing	0.999	D	0.603	neutral	D	0.530698433	None	None	N
N/E	0.9972	likely_pathogenic	0.9973	pathogenic	-1.168	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
N/F	0.9994	likely_pathogenic	0.9995	pathogenic	-0.958	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
N/G	0.9829	likely_pathogenic	0.9849	pathogenic	-1.019	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
N/H	0.9756	likely_pathogenic	0.9801	pathogenic	-0.909	Destabilizing	1.0	D	0.733	prob.delet.	D	0.563895204	None	None	N
N/I	0.9938	likely_pathogenic	0.9946	pathogenic	-0.192	Destabilizing	1.0	D	0.724	prob.delet.	D	0.564148693	None	None	N
N/K	0.9981	likely_pathogenic	0.9984	pathogenic	-0.119	Destabilizing	1.0	D	0.733	prob.delet.	D	0.545283969	None	None	N
N/L	0.9926	likely_pathogenic	0.9936	pathogenic	-0.192	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
N/M	0.9939	likely_pathogenic	0.9953	pathogenic	0.406	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
N/P	0.9983	likely_pathogenic	0.9981	pathogenic	-0.361	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
N/Q	0.9979	likely_pathogenic	0.9982	pathogenic	-1.023	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
N/R	0.9979	likely_pathogenic	0.9979	pathogenic	0.077	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/S	0.8426	likely_pathogenic	0.8671	pathogenic	-0.708	Destabilizing	0.999	D	0.567	neutral	N	0.518163586	None	None	N
N/T	0.9475	likely_pathogenic	0.9609	pathogenic	-0.509	Destabilizing	0.999	D	0.701	prob.neutral	D	0.54477699	None	None	N
N/V	0.993	likely_pathogenic	0.9938	pathogenic	-0.361	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
N/W	0.9997	likely_pathogenic	0.9997	pathogenic	-0.764	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
N/Y	0.9869	likely_pathogenic	0.9887	pathogenic	-0.477	Destabilizing	1.0	D	0.748	deleterious	D	0.552538898	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.