TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18345	55258;55259;55260	chr2:178602369;178602368;178602367	chr2:179467096;179467095;179467094
N2AB	16704	50335;50336;50337	chr2:178602369;178602368;178602367	chr2:179467096;179467095;179467094
N2A	15777	47554;47555;47556	chr2:178602369;178602368;178602367	chr2:179467096;179467095;179467094
N2B	9280	28063;28064;28065	chr2:178602369;178602368;178602367	chr2:179467096;179467095;179467094
Novex-1	9405	28438;28439;28440	chr2:178602369;178602368;178602367	chr2:179467096;179467095;179467094
Novex-2	9472	28639;28640;28641	chr2:178602369;178602368;178602367	chr2:179467096;179467095;179467094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-21
• Domain position: 74
• Structural Position: 104
• Q(SASA): 0.1139
• 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
Y/H	rs2053680681	None	0.391	D	0.607	0.805	0.630093501459	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
Y/H	rs2053680681	None	0.391	D	0.607	0.805	0.630093501459	gnomAD-4.0.0	6.57955E-06	None	None	None	None	N	None	0	6.56426E-05	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
Y/A	0.9798	likely_pathogenic	0.9807	pathogenic	-3.289	Highly Destabilizing	0.996	D	0.816	deleterious	None	None	None	None	N
Y/C	0.7166	likely_pathogenic	0.7242	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.819	deleterious	D	0.645076136	None	None	N
Y/D	0.988	likely_pathogenic	0.9901	pathogenic	-3.942	Highly Destabilizing	0.998	D	0.855	deleterious	D	0.677347023	None	None	N
Y/E	0.9951	likely_pathogenic	0.9956	pathogenic	-3.728	Highly Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
Y/F	0.2381	likely_benign	0.2481	benign	-1.348	Destabilizing	0.994	D	0.717	prob.delet.	D	0.6084352	None	None	N
Y/G	0.9482	likely_pathogenic	0.9545	pathogenic	-3.698	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
Y/H	0.9158	likely_pathogenic	0.9209	pathogenic	-2.427	Highly Destabilizing	0.391	N	0.607	neutral	D	0.651808911	None	None	N
Y/I	0.9428	likely_pathogenic	0.9395	pathogenic	-1.903	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/K	0.9951	likely_pathogenic	0.9952	pathogenic	-2.639	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
Y/L	0.9261	likely_pathogenic	0.9163	pathogenic	-1.903	Destabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
Y/M	0.9603	likely_pathogenic	0.9609	pathogenic	-1.615	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/N	0.903	likely_pathogenic	0.9114	pathogenic	-3.528	Highly Destabilizing	0.997	D	0.837	deleterious	D	0.677145219	None	None	N
Y/P	0.9976	likely_pathogenic	0.9981	pathogenic	-2.384	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/Q	0.991	likely_pathogenic	0.9916	pathogenic	-3.242	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
Y/R	0.9866	likely_pathogenic	0.9867	pathogenic	-2.43	Highly Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	N
Y/S	0.9572	likely_pathogenic	0.9623	pathogenic	-3.791	Highly Destabilizing	0.998	D	0.835	deleterious	D	0.677347023	None	None	N
Y/T	0.9829	likely_pathogenic	0.9836	pathogenic	-3.457	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/V	0.8942	likely_pathogenic	0.8928	pathogenic	-2.384	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/W	0.764	likely_pathogenic	0.7894	pathogenic	-0.683	Destabilizing	1.0	D	0.764	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.