TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19994	60205;60206;60207	chr2:178591839;178591838;178591837	chr2:179456566;179456565;179456564
N2AB	18353	55282;55283;55284	chr2:178591839;178591838;178591837	chr2:179456566;179456565;179456564
N2A	17426	52501;52502;52503	chr2:178591839;178591838;178591837	chr2:179456566;179456565;179456564
N2B	10929	33010;33011;33012	chr2:178591839;178591838;178591837	chr2:179456566;179456565;179456564
Novex-1	11054	33385;33386;33387	chr2:178591839;178591838;178591837	chr2:179456566;179456565;179456564
Novex-2	11121	33586;33587;33588	chr2:178591839;178591838;178591837	chr2:179456566;179456565;179456564
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-33
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0845
• 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/D	None	None	1.0	D	0.873	0.64	0.789897024495	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	0.7372	likely_pathogenic	0.6835	pathogenic	-2.3	Highly Destabilizing	0.999	D	0.599	neutral	N	0.506957873	None	None	N
V/C	0.952	likely_pathogenic	0.944	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.9973	pathogenic	-3.432	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.533904892	None	None	N
V/E	0.9933	likely_pathogenic	0.9945	pathogenic	-3.135	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/F	0.9237	likely_pathogenic	0.9199	pathogenic	-1.23	Destabilizing	1.0	D	0.867	deleterious	N	0.499440674	None	None	N
V/G	0.8965	likely_pathogenic	0.8872	pathogenic	-2.897	Highly Destabilizing	1.0	D	0.864	deleterious	N	0.510178323	None	None	N
V/H	0.9983	likely_pathogenic	0.9985	pathogenic	-2.8	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1443	likely_benign	0.1358	benign	-0.571	Destabilizing	0.997	D	0.502	neutral	N	0.469111561	None	None	N
V/K	0.9955	likely_pathogenic	0.9966	pathogenic	-1.914	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.8361	likely_pathogenic	0.8047	pathogenic	-0.571	Destabilizing	0.997	D	0.595	neutral	N	0.511723401	None	None	N
V/M	0.8326	likely_pathogenic	0.8075	pathogenic	-0.918	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
V/N	0.9901	likely_pathogenic	0.9906	pathogenic	-2.541	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/P	0.9979	likely_pathogenic	0.9979	pathogenic	-1.127	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/Q	0.9934	likely_pathogenic	0.9944	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/R	0.9911	likely_pathogenic	0.993	pathogenic	-1.931	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/S	0.9609	likely_pathogenic	0.9555	pathogenic	-3.071	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/T	0.893	likely_pathogenic	0.885	pathogenic	-2.622	Highly Destabilizing	0.999	D	0.612	neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.999	pathogenic	-1.88	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9896	likely_pathogenic	0.9898	pathogenic	-1.541	Destabilizing	1.0	D	0.879	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.