TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2325	7198;7199;7200	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016
N2AB	2325	7198;7199;7200	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016
N2A	2325	7198;7199;7200	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016
N2B	2279	7060;7061;7062	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016
Novex-1	2279	7060;7061;7062	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016
Novex-2	2279	7060;7061;7062	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016
Novex-3	2325	7198;7199;7200	chr2:178774291;178774290;178774289	chr2:179639018;179639017;179639016

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-12
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.1027
• 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
V/G	None	None	0.997	N	0.877	0.727	0.920123548367	gnomAD-4.0.0	1.59058E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85672E-06	0	0
V/I	None	None	0.046	N	0.281	0.159	0.292423486923	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.8734	likely_pathogenic	0.8798	pathogenic	-2.258	Highly Destabilizing	0.939	D	0.609	neutral	N	0.507688082	None	None	N
V/C	0.9593	likely_pathogenic	0.963	pathogenic	-1.79	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9983	pathogenic	-3.015	Highly Destabilizing	0.997	D	0.877	deleterious	N	0.509190191	None	None	N
V/E	0.9909	likely_pathogenic	0.9916	pathogenic	-2.684	Highly Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
V/F	0.6643	likely_pathogenic	0.6796	pathogenic	-1.31	Destabilizing	0.982	D	0.828	deleterious	N	0.511093416	None	None	N
V/G	0.9608	likely_pathogenic	0.9651	pathogenic	-2.899	Highly Destabilizing	0.997	D	0.877	deleterious	N	0.509190191	None	None	N
V/H	0.9948	likely_pathogenic	0.9953	pathogenic	-2.855	Highly Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
V/I	0.074	likely_benign	0.0772	benign	-0.397	Destabilizing	0.046	N	0.281	neutral	N	0.331040381	None	None	N
V/K	0.9893	likely_pathogenic	0.9895	pathogenic	-1.743	Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
V/L	0.3871	ambiguous	0.4097	ambiguous	-0.397	Destabilizing	0.76	D	0.509	neutral	N	0.49358547	None	None	N
V/M	0.4516	ambiguous	0.4694	ambiguous	-0.692	Destabilizing	0.986	D	0.707	prob.neutral	None	None	None	None	N
V/N	0.99	likely_pathogenic	0.9917	pathogenic	-2.43	Highly Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
V/P	0.9954	likely_pathogenic	0.9963	pathogenic	-0.997	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
V/Q	0.9872	likely_pathogenic	0.9881	pathogenic	-2.034	Highly Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
V/R	0.9827	likely_pathogenic	0.9836	pathogenic	-1.942	Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
V/S	0.9712	likely_pathogenic	0.9749	pathogenic	-3.011	Highly Destabilizing	0.993	D	0.869	deleterious	None	None	None	None	N
V/T	0.933	likely_pathogenic	0.9371	pathogenic	-2.502	Highly Destabilizing	0.953	D	0.719	prob.delet.	None	None	None	None	N
V/W	0.9939	likely_pathogenic	0.9946	pathogenic	-1.856	Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
V/Y	0.9734	likely_pathogenic	0.9758	pathogenic	-1.502	Destabilizing	0.998	D	0.823	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.