TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33724	101395;101396;101397	chr2:178535445;178535444;178535443	chr2:179400172;179400171;179400170
N2AB	32083	96472;96473;96474	chr2:178535445;178535444;178535443	chr2:179400172;179400171;179400170
N2A	31156	93691;93692;93693	chr2:178535445;178535444;178535443	chr2:179400172;179400171;179400170
N2B	24659	74200;74201;74202	chr2:178535445;178535444;178535443	chr2:179400172;179400171;179400170
Novex-1	24784	74575;74576;74577	chr2:178535445;178535444;178535443	chr2:179400172;179400171;179400170
Novex-2	24851	74776;74777;74778	chr2:178535445;178535444;178535443	chr2:179400172;179400171;179400170
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: Fn3-132
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1176
• 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/C	None	None	1.0	D	0.839	0.873	0.873223006722	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9979	likely_pathogenic	0.997	pathogenic	-3.586	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
Y/C	0.9503	likely_pathogenic	0.9344	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.639954256	None	None	N
Y/D	0.9972	likely_pathogenic	0.9964	pathogenic	-3.875	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.656175422	None	None	N
Y/E	0.9995	likely_pathogenic	0.9992	pathogenic	-3.679	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/F	0.2975	likely_benign	0.2714	benign	-1.383	Destabilizing	1.0	D	0.638	neutral	D	0.548917147	None	None	N
Y/G	0.9953	likely_pathogenic	0.9934	pathogenic	-3.96	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/H	0.9747	likely_pathogenic	0.9691	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.8	deleterious	D	0.639752452	None	None	N
Y/I	0.9818	likely_pathogenic	0.9707	pathogenic	-2.311	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.998	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/L	0.9608	likely_pathogenic	0.9479	pathogenic	-2.311	Highly Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Y/M	0.9907	likely_pathogenic	0.9865	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/N	0.9837	likely_pathogenic	0.9785	pathogenic	-3.203	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.656175422	None	None	N
Y/P	0.9997	likely_pathogenic	0.9996	pathogenic	-2.756	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.9983	pathogenic	-2.991	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/R	0.9949	likely_pathogenic	0.9919	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/S	0.9922	likely_pathogenic	0.9888	pathogenic	-3.507	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.640156061	None	None	N
Y/T	0.9962	likely_pathogenic	0.9943	pathogenic	-3.205	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/V	0.9661	likely_pathogenic	0.95	pathogenic	-2.756	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/W	0.8792	likely_pathogenic	0.8652	pathogenic	-0.648	Destabilizing	1.0	D	0.792	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.