TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6408	19447;19448;19449	chr2:178728704;178728703;178728702	chr2:179593431;179593430;179593429
N2AB	6091	18496;18497;18498	chr2:178728704;178728703;178728702	chr2:179593431;179593430;179593429
N2A	5164	15715;15716;15717	chr2:178728704;178728703;178728702	chr2:179593431;179593430;179593429
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-48
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1001
• 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/A	None	None	0.999	D	0.613	0.612	0.706496497531	gnomAD-4.0.0	6.84496E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15966E-05	0
V/G	None	None	1.0	D	0.857	0.836	0.882822177023	gnomAD-4.0.0	1.36899E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79961E-06	0	0
V/M	rs2154306642	None	1.0	D	0.767	0.589	0.739150905744	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

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	0.5739	likely_pathogenic	0.5155	ambiguous	-1.965	Destabilizing	0.999	D	0.613	neutral	D	0.535838851	None	None	N
V/C	0.9768	likely_pathogenic	0.9781	pathogenic	-1.422	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.998	pathogenic	-2.761	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/E	0.9892	likely_pathogenic	0.9922	pathogenic	-2.506	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.631733873	None	None	N
V/F	0.8005	likely_pathogenic	0.8032	pathogenic	-1.162	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/G	0.8837	likely_pathogenic	0.9031	pathogenic	-2.535	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.57415704	None	None	N
V/H	0.9967	likely_pathogenic	0.9977	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.1478	likely_benign	0.1436	benign	-0.359	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
V/K	0.9934	likely_pathogenic	0.9956	pathogenic	-1.715	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/L	0.7087	likely_pathogenic	0.7347	pathogenic	-0.359	Destabilizing	0.997	D	0.629	neutral	D	0.544248878	None	None	N
V/M	0.7296	likely_pathogenic	0.7229	pathogenic	-0.381	Destabilizing	1.0	D	0.767	deleterious	D	0.631330265	None	None	N
V/N	0.9928	likely_pathogenic	0.9946	pathogenic	-2.167	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/P	0.9859	likely_pathogenic	0.9909	pathogenic	-0.868	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/Q	0.9895	likely_pathogenic	0.9915	pathogenic	-1.934	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/R	0.9847	likely_pathogenic	0.9897	pathogenic	-1.647	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/S	0.9149	likely_pathogenic	0.9126	pathogenic	-2.745	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/T	0.7318	likely_pathogenic	0.7035	pathogenic	-2.339	Highly Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
V/W	0.9973	likely_pathogenic	0.998	pathogenic	-1.784	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/Y	0.989	likely_pathogenic	0.9905	pathogenic	-1.335	Destabilizing	1.0	D	0.841	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.