TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16033	48322;48323;48324	chr2:178616792;178616791;178616790	chr2:179481519;179481518;179481517
N2AB	14392	43399;43400;43401	chr2:178616792;178616791;178616790	chr2:179481519;179481518;179481517
N2A	13465	40618;40619;40620	chr2:178616792;178616791;178616790	chr2:179481519;179481518;179481517
N2B	6968	21127;21128;21129	chr2:178616792;178616791;178616790	chr2:179481519;179481518;179481517
Novex-1	7093	21502;21503;21504	chr2:178616792;178616791;178616790	chr2:179481519;179481518;179481517
Novex-2	7160	21703;21704;21705	chr2:178616792;178616791;178616790	chr2:179481519;179481518;179481517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-109
• Domain position: 66
• Structural Position: 154
• Q(SASA): 0.0953
• 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	None	None	1.0	D	0.787	0.857	0.645390446725	gnomAD-4.0.0	1.59323E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	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	0.9969	likely_pathogenic	0.9978	pathogenic	-1.375	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
Y/C	0.9196	likely_pathogenic	0.9422	pathogenic	-0.768	Destabilizing	1.0	D	0.814	deleterious	D	0.722410158	None	None	N
Y/D	0.9983	likely_pathogenic	0.999	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.722410158	None	None	N
Y/E	0.9993	likely_pathogenic	0.9996	pathogenic	-1.855	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/F	0.2529	likely_benign	0.2606	benign	-0.257	Destabilizing	0.999	D	0.696	prob.neutral	D	0.627058985	None	None	N
Y/G	0.9939	likely_pathogenic	0.9955	pathogenic	-1.808	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/H	0.968	likely_pathogenic	0.9786	pathogenic	-1.639	Destabilizing	1.0	D	0.787	deleterious	D	0.723017958	None	None	N
Y/I	0.9552	likely_pathogenic	0.9625	pathogenic	0.039	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.999	pathogenic	-1.182	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/L	0.8851	likely_pathogenic	0.8908	pathogenic	0.039	Stabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
Y/M	0.9866	likely_pathogenic	0.9887	pathogenic	-0.105	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/N	0.9918	likely_pathogenic	0.9946	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.722410158	None	None	N
Y/P	0.9975	likely_pathogenic	0.9982	pathogenic	-0.444	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/Q	0.9985	likely_pathogenic	0.9991	pathogenic	-1.536	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
Y/R	0.9911	likely_pathogenic	0.994	pathogenic	-1.793	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/S	0.9912	likely_pathogenic	0.9942	pathogenic	-2.31	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.722410158	None	None	N
Y/T	0.9971	likely_pathogenic	0.9981	pathogenic	-1.911	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/V	0.9367	likely_pathogenic	0.9474	pathogenic	-0.444	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
Y/W	0.7699	likely_pathogenic	0.7939	pathogenic	0.233	Stabilizing	1.0	D	0.774	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.