TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26787	80584;80585;80586	chr2:178565773;178565772;178565771	chr2:179430500;179430499;179430498
N2AB	25146	75661;75662;75663	chr2:178565773;178565772;178565771	chr2:179430500;179430499;179430498
N2A	24219	72880;72881;72882	chr2:178565773;178565772;178565771	chr2:179430500;179430499;179430498
N2B	17722	53389;53390;53391	chr2:178565773;178565772;178565771	chr2:179430500;179430499;179430498
Novex-1	17847	53764;53765;53766	chr2:178565773;178565772;178565771	chr2:179430500;179430499;179430498
Novex-2	17914	53965;53966;53967	chr2:178565773;178565772;178565771	chr2:179430500;179430499;179430498
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-83
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2208
• 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/F	None	None	0.942	N	0.771	0.281	0.639482846592	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
V/I	None	None	0.014	N	0.423	0.047	0.344483371355	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	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
V/A	0.8273	likely_pathogenic	0.8117	pathogenic	-1.998	Destabilizing	0.014	N	0.383	neutral	N	0.482179646	None	None	N
V/C	0.952	likely_pathogenic	0.9485	pathogenic	-1.537	Destabilizing	0.994	D	0.727	prob.delet.	None	None	None	None	N
V/D	0.9885	likely_pathogenic	0.9862	pathogenic	-2.634	Highly Destabilizing	0.942	D	0.809	deleterious	N	0.489062328	None	None	N
V/E	0.9751	likely_pathogenic	0.9733	pathogenic	-2.471	Highly Destabilizing	0.956	D	0.772	deleterious	None	None	None	None	N
V/F	0.7209	likely_pathogenic	0.6716	pathogenic	-1.2	Destabilizing	0.942	D	0.771	deleterious	N	0.496839667	None	None	N
V/G	0.8419	likely_pathogenic	0.8212	pathogenic	-2.484	Highly Destabilizing	0.014	N	0.523	neutral	N	0.478466491	None	None	N
V/H	0.9939	likely_pathogenic	0.9937	pathogenic	-2.284	Highly Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
V/I	0.0895	likely_benign	0.0936	benign	-0.668	Destabilizing	0.014	N	0.423	neutral	N	0.455646405	None	None	N
V/K	0.9858	likely_pathogenic	0.9859	pathogenic	-1.816	Destabilizing	0.956	D	0.778	deleterious	None	None	None	None	N
V/L	0.3923	ambiguous	0.4262	ambiguous	-0.668	Destabilizing	0.489	N	0.733	prob.delet.	N	0.384044518	None	None	N
V/M	0.5221	ambiguous	0.5115	ambiguous	-0.664	Destabilizing	0.956	D	0.699	prob.neutral	None	None	None	None	N
V/N	0.9615	likely_pathogenic	0.9576	pathogenic	-1.969	Destabilizing	0.956	D	0.817	deleterious	None	None	None	None	N
V/P	0.9333	likely_pathogenic	0.9372	pathogenic	-1.083	Destabilizing	0.978	D	0.79	deleterious	None	None	None	None	N
V/Q	0.9803	likely_pathogenic	0.9807	pathogenic	-1.896	Destabilizing	0.978	D	0.779	deleterious	None	None	None	None	N
V/R	0.9804	likely_pathogenic	0.9811	pathogenic	-1.536	Destabilizing	0.978	D	0.821	deleterious	None	None	None	None	N
V/S	0.9463	likely_pathogenic	0.9383	pathogenic	-2.526	Highly Destabilizing	0.754	D	0.753	deleterious	None	None	None	None	N
V/T	0.8905	likely_pathogenic	0.8894	pathogenic	-2.238	Highly Destabilizing	0.86	D	0.746	deleterious	None	None	None	None	N
V/W	0.9918	likely_pathogenic	0.9894	pathogenic	-1.723	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
V/Y	0.9656	likely_pathogenic	0.9592	pathogenic	-1.357	Destabilizing	0.993	D	0.748	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.