TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28447	85564;85565;85566	chr2:178560793;178560792;178560791	chr2:179425520;179425519;179425518
N2AB	26806	80641;80642;80643	chr2:178560793;178560792;178560791	chr2:179425520;179425519;179425518
N2A	25879	77860;77861;77862	chr2:178560793;178560792;178560791	chr2:179425520;179425519;179425518
N2B	19382	58369;58370;58371	chr2:178560793;178560792;178560791	chr2:179425520;179425519;179425518
Novex-1	19507	58744;58745;58746	chr2:178560793;178560792;178560791	chr2:179425520;179425519;179425518
Novex-2	19574	58945;58946;58947	chr2:178560793;178560792;178560791	chr2:179425520;179425519;179425518
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-143
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.3069
• Predicted PPI site: I

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/L	rs1269228304	-0.68	0.476	D	0.723	0.583	0.437420747294	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/L	rs1269228304	-0.68	0.476	D	0.723	0.583	0.437420747294	gnomAD-4.0.0	3.18315E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	3.02499E-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	0.9154	likely_pathogenic	0.9127	pathogenic	-1.872	Destabilizing	0.928	D	0.727	prob.delet.	D	0.627340592	None	None	I
V/C	0.9822	likely_pathogenic	0.9827	pathogenic	-1.498	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	I
V/D	0.993	likely_pathogenic	0.9946	pathogenic	-2.404	Highly Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	I
V/E	0.9832	likely_pathogenic	0.9875	pathogenic	-2.379	Highly Destabilizing	0.996	D	0.84	deleterious	D	0.627946005	None	None	I
V/F	0.8646	likely_pathogenic	0.8907	pathogenic	-1.502	Destabilizing	0.983	D	0.859	deleterious	None	None	None	None	I
V/G	0.9177	likely_pathogenic	0.9212	pathogenic	-2.216	Highly Destabilizing	0.989	D	0.829	deleterious	D	0.627946005	None	None	I
V/H	0.9955	likely_pathogenic	0.9965	pathogenic	-1.747	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
V/I	0.1233	likely_benign	0.1265	benign	-0.996	Destabilizing	0.039	N	0.544	neutral	N	0.515296653	None	None	I
V/K	0.9865	likely_pathogenic	0.9909	pathogenic	-1.595	Destabilizing	0.992	D	0.839	deleterious	None	None	None	None	I
V/L	0.8349	likely_pathogenic	0.8454	pathogenic	-0.996	Destabilizing	0.476	N	0.723	prob.delet.	D	0.625322549	None	None	I
V/M	0.8448	likely_pathogenic	0.8552	pathogenic	-0.812	Destabilizing	0.983	D	0.872	deleterious	None	None	None	None	I
V/N	0.9787	likely_pathogenic	0.9817	pathogenic	-1.533	Destabilizing	0.997	D	0.851	deleterious	None	None	None	None	I
V/P	0.9837	likely_pathogenic	0.9859	pathogenic	-1.257	Destabilizing	0.997	D	0.845	deleterious	None	None	None	None	I
V/Q	0.9848	likely_pathogenic	0.9891	pathogenic	-1.721	Destabilizing	0.997	D	0.854	deleterious	None	None	None	None	I
V/R	0.9744	likely_pathogenic	0.9821	pathogenic	-1.041	Destabilizing	0.997	D	0.849	deleterious	None	None	None	None	I
V/S	0.9579	likely_pathogenic	0.96	pathogenic	-2.017	Highly Destabilizing	0.992	D	0.831	deleterious	None	None	None	None	I
V/T	0.9391	likely_pathogenic	0.9421	pathogenic	-1.888	Destabilizing	0.944	D	0.817	deleterious	None	None	None	None	I
V/W	0.9981	likely_pathogenic	0.9984	pathogenic	-1.751	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	I
V/Y	0.9808	likely_pathogenic	0.9854	pathogenic	-1.469	Destabilizing	0.992	D	0.857	deleterious	None	None	None	None	I

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.