TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20938	63037;63038;63039	chr2:178588913;178588912;178588911	chr2:179453640;179453639;179453638
N2AB	19297	58114;58115;58116	chr2:178588913;178588912;178588911	chr2:179453640;179453639;179453638
N2A	18370	55333;55334;55335	chr2:178588913;178588912;178588911	chr2:179453640;179453639;179453638
N2B	11873	35842;35843;35844	chr2:178588913;178588912;178588911	chr2:179453640;179453639;179453638
Novex-1	11998	36217;36218;36219	chr2:178588913;178588912;178588911	chr2:179453640;179453639;179453638
Novex-2	12065	36418;36419;36420	chr2:178588913;178588912;178588911	chr2:179453640;179453639;179453638
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: Fn3-39
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0692
• 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	0.928	D	0.899	0.765	0.86557087108	gnomAD-4.0.0	1.59295E-06	None	None	None	None	N	None	5.66187E-05	0	None	0	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	0.8218	likely_pathogenic	0.8264	pathogenic	-2.619	Highly Destabilizing	0.645	D	0.622	neutral	D	0.547212749	None	None	N
V/C	0.9438	likely_pathogenic	0.9484	pathogenic	-2.06	Highly Destabilizing	0.995	D	0.743	deleterious	None	None	None	None	N
V/D	0.9991	likely_pathogenic	0.9989	pathogenic	-3.576	Highly Destabilizing	0.928	D	0.899	deleterious	D	0.632966136	None	None	N
V/E	0.9969	likely_pathogenic	0.9961	pathogenic	-3.268	Highly Destabilizing	0.945	D	0.864	deleterious	None	None	None	None	N
V/F	0.948	likely_pathogenic	0.922	pathogenic	-1.468	Destabilizing	0.864	D	0.753	deleterious	D	0.558569054	None	None	N
V/G	0.9001	likely_pathogenic	0.8928	pathogenic	-3.189	Highly Destabilizing	0.928	D	0.888	deleterious	D	0.632966136	None	None	N
V/H	0.9992	likely_pathogenic	0.9989	pathogenic	-2.993	Highly Destabilizing	0.995	D	0.874	deleterious	None	None	None	None	N
V/I	0.1143	likely_benign	0.1106	benign	-0.944	Destabilizing	0.006	N	0.265	neutral	N	0.495259252	None	None	N
V/K	0.9977	likely_pathogenic	0.9968	pathogenic	-2.206	Highly Destabilizing	0.945	D	0.863	deleterious	None	None	None	None	N
V/L	0.6778	likely_pathogenic	0.6024	pathogenic	-0.944	Destabilizing	0.006	N	0.311	neutral	D	0.536408967	None	None	N
V/M	0.8508	likely_pathogenic	0.805	pathogenic	-1.24	Destabilizing	0.894	D	0.658	neutral	None	None	None	None	N
V/N	0.9961	likely_pathogenic	0.9954	pathogenic	-2.867	Highly Destabilizing	0.981	D	0.911	deleterious	None	None	None	None	N
V/P	0.9957	likely_pathogenic	0.9955	pathogenic	-1.488	Destabilizing	0.981	D	0.88	deleterious	None	None	None	None	N
V/Q	0.9959	likely_pathogenic	0.9946	pathogenic	-2.53	Highly Destabilizing	0.981	D	0.897	deleterious	None	None	None	None	N
V/R	0.9947	likely_pathogenic	0.9932	pathogenic	-2.204	Highly Destabilizing	0.945	D	0.909	deleterious	None	None	None	None	N
V/S	0.9707	likely_pathogenic	0.9725	pathogenic	-3.34	Highly Destabilizing	0.945	D	0.844	deleterious	None	None	None	None	N
V/T	0.9296	likely_pathogenic	0.9305	pathogenic	-2.889	Highly Destabilizing	0.707	D	0.631	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.999	pathogenic	-2.021	Highly Destabilizing	0.995	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9954	likely_pathogenic	0.9931	pathogenic	-1.779	Destabilizing	0.945	D	0.746	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.