TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14876	44851;44852;44853	chr2:178624654;178624653;178624652	chr2:179489381;179489380;179489379
N2AB	13235	39928;39929;39930	chr2:178624654;178624653;178624652	chr2:179489381;179489380;179489379
N2A	12308	37147;37148;37149	chr2:178624654;178624653;178624652	chr2:179489381;179489380;179489379
N2B	5811	17656;17657;17658	chr2:178624654;178624653;178624652	chr2:179489381;179489380;179489379
Novex-1	5936	18031;18032;18033	chr2:178624654;178624653;178624652	chr2:179489381;179489380;179489379
Novex-2	6003	18232;18233;18234	chr2:178624654;178624653;178624652	chr2:179489381;179489380;179489379
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: Ig-100
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.073
• 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	0.983	D	0.845	0.71	0.933483574898	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.8638	likely_pathogenic	0.8745	pathogenic	-2.266	Highly Destabilizing	0.892	D	0.625	neutral	D	0.533128328	None	None	N
V/C	0.981	likely_pathogenic	0.9807	pathogenic	-2.302	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
V/D	0.9833	likely_pathogenic	0.9871	pathogenic	-3.231	Highly Destabilizing	0.994	D	0.842	deleterious	D	0.753626676	None	None	N
V/E	0.9766	likely_pathogenic	0.9771	pathogenic	-3.076	Highly Destabilizing	0.987	D	0.82	deleterious	None	None	None	None	N
V/F	0.8556	likely_pathogenic	0.8174	pathogenic	-1.384	Destabilizing	0.967	D	0.796	deleterious	D	0.648341842	None	None	N
V/G	0.8129	likely_pathogenic	0.8366	pathogenic	-2.715	Highly Destabilizing	0.983	D	0.845	deleterious	D	0.73227802	None	None	N
V/H	0.9958	likely_pathogenic	0.9953	pathogenic	-2.133	Highly Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
V/I	0.1631	likely_benign	0.1609	benign	-1.029	Destabilizing	0.099	N	0.303	neutral	N	0.519202001	None	None	N
V/K	0.9876	likely_pathogenic	0.988	pathogenic	-1.902	Destabilizing	0.987	D	0.821	deleterious	None	None	None	None	N
V/L	0.565	likely_pathogenic	0.5486	ambiguous	-1.029	Destabilizing	0.025	N	0.345	neutral	N	0.510107023	None	None	N
V/M	0.7577	likely_pathogenic	0.7225	pathogenic	-1.293	Destabilizing	0.975	D	0.721	prob.delet.	None	None	None	None	N
V/N	0.9644	likely_pathogenic	0.9689	pathogenic	-2.216	Highly Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
V/P	0.9867	likely_pathogenic	0.9892	pathogenic	-1.416	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9874	likely_pathogenic	0.9874	pathogenic	-2.206	Highly Destabilizing	0.996	D	0.822	deleterious	None	None	None	None	N
V/R	0.9822	likely_pathogenic	0.982	pathogenic	-1.522	Destabilizing	0.987	D	0.847	deleterious	None	None	None	None	N
V/S	0.9455	likely_pathogenic	0.9505	pathogenic	-2.773	Highly Destabilizing	0.987	D	0.815	deleterious	None	None	None	None	N
V/T	0.7555	likely_pathogenic	0.7796	pathogenic	-2.494	Highly Destabilizing	0.916	D	0.675	prob.neutral	None	None	None	None	N
V/W	0.9979	likely_pathogenic	0.9973	pathogenic	-1.758	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
V/Y	0.9826	likely_pathogenic	0.9787	pathogenic	-1.492	Destabilizing	0.987	D	0.779	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.