TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6315	19168;19169;19170	chr2:178729095;178729094;178729093	chr2:179593822;179593821;179593820
N2AB	5998	18217;18218;18219	chr2:178729095;178729094;178729093	chr2:179593822;179593821;179593820
N2A	5071	15436;15437;15438	chr2:178729095;178729094;178729093	chr2:179593822;179593821;179593820
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-47
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1431
• 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/M	rs770552574	-0.461	0.996	D	0.787	0.529	0.617849357852	gnomAD-2.1.1	1.64E-05	None	None	None	None	N	None	0	0	None	0	1.13507E-04	None	6.66E-05	None	0	0	0
V/M	rs770552574	-0.461	0.996	D	0.787	0.529	0.617849357852	gnomAD-4.0.0	1.37044E-05	None	None	None	None	N	None	0	0	None	0	5.05663E-05	None	0	0	1.35023E-05	3.49577E-05	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	0.4801	ambiguous	0.5751	pathogenic	-1.613	Destabilizing	0.928	D	0.613	neutral	N	0.515906296	None	None	N
V/C	0.9411	likely_pathogenic	0.9522	pathogenic	-1.398	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
V/D	0.9895	likely_pathogenic	0.9938	pathogenic	-1.053	Destabilizing	0.997	D	0.877	deleterious	None	None	None	None	N
V/E	0.9644	likely_pathogenic	0.9756	pathogenic	-0.863	Destabilizing	0.996	D	0.864	deleterious	D	0.627322745	None	None	N
V/F	0.4186	ambiguous	0.4322	ambiguous	-0.898	Destabilizing	0.983	D	0.847	deleterious	None	None	None	None	N
V/G	0.8186	likely_pathogenic	0.8748	pathogenic	-2.117	Highly Destabilizing	0.989	D	0.869	deleterious	D	0.595284023	None	None	N
V/H	0.9822	likely_pathogenic	0.9859	pathogenic	-1.729	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/I	0.0929	likely_benign	0.0898	benign	-0.238	Destabilizing	0.05	N	0.269	neutral	None	None	None	None	N
V/K	0.9687	likely_pathogenic	0.976	pathogenic	-0.985	Destabilizing	0.992	D	0.865	deleterious	None	None	None	None	N
V/L	0.3331	likely_benign	0.3953	ambiguous	-0.238	Destabilizing	0.698	D	0.619	neutral	D	0.57612662	None	None	N
V/M	0.3169	likely_benign	0.3887	ambiguous	-0.51	Destabilizing	0.996	D	0.787	deleterious	D	0.601381025	None	None	N
V/N	0.9612	likely_pathogenic	0.9752	pathogenic	-1.144	Destabilizing	0.997	D	0.901	deleterious	None	None	None	None	N
V/P	0.9708	likely_pathogenic	0.9789	pathogenic	-0.666	Destabilizing	0.997	D	0.869	deleterious	None	None	None	None	N
V/Q	0.9573	likely_pathogenic	0.9677	pathogenic	-0.987	Destabilizing	0.997	D	0.889	deleterious	None	None	None	None	N
V/R	0.949	likely_pathogenic	0.9597	pathogenic	-0.984	Destabilizing	0.997	D	0.896	deleterious	None	None	None	None	N
V/S	0.827	likely_pathogenic	0.8813	pathogenic	-1.95	Destabilizing	0.992	D	0.857	deleterious	None	None	None	None	N
V/T	0.547	ambiguous	0.6533	pathogenic	-1.602	Destabilizing	0.944	D	0.684	prob.neutral	None	None	None	None	N
V/W	0.9789	likely_pathogenic	0.9813	pathogenic	-1.2	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9121	likely_pathogenic	0.9224	pathogenic	-0.82	Destabilizing	0.992	D	0.846	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.