TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6022	18289;18290;18291	chr2:178730336;178730335;178730334	chr2:179595063;179595062;179595061
N2AB	5705	17338;17339;17340	chr2:178730336;178730335;178730334	chr2:179595063;179595062;179595061
N2A	4778	14557;14558;14559	chr2:178730336;178730335;178730334	chr2:179595063;179595062;179595061
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-44
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.6693
• 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
D/N	rs767465221	0.173	0.046	N	0.131	0.166	0.215109475489	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.69E-05	0	0
D/N	rs767465221	0.173	0.046	N	0.131	0.166	0.215109475489	gnomAD-4.0.0	1.60502E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88736E-05	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
D/A	0.1777	likely_benign	0.1536	benign	-0.383	Destabilizing	0.896	D	0.535	neutral	N	0.484398806	None	None	N
D/C	0.7048	likely_pathogenic	0.662	pathogenic	-0.227	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
D/E	0.1532	likely_benign	0.1487	benign	-0.385	Destabilizing	0.026	N	0.135	neutral	N	0.460308438	None	None	N
D/F	0.563	ambiguous	0.5185	ambiguous	0.142	Stabilizing	0.996	D	0.671	neutral	None	None	None	None	N
D/G	0.2725	likely_benign	0.2337	benign	-0.686	Destabilizing	0.896	D	0.539	neutral	N	0.519455529	None	None	N
D/H	0.3207	likely_benign	0.2861	benign	0.177	Stabilizing	0.984	D	0.567	neutral	N	0.519628887	None	None	N
D/I	0.2647	likely_benign	0.2529	benign	0.402	Stabilizing	0.988	D	0.661	neutral	None	None	None	None	N
D/K	0.424	ambiguous	0.37	ambiguous	0.041	Stabilizing	0.851	D	0.519	neutral	None	None	None	None	N
D/L	0.3536	ambiguous	0.3249	benign	0.402	Stabilizing	0.976	D	0.619	neutral	None	None	None	None	N
D/M	0.5396	ambiguous	0.5102	ambiguous	0.528	Stabilizing	0.999	D	0.662	neutral	None	None	None	None	N
D/N	0.1177	likely_benign	0.1094	benign	-0.537	Destabilizing	0.046	N	0.131	neutral	N	0.460753942	None	None	N
D/P	0.7539	likely_pathogenic	0.6966	pathogenic	0.165	Stabilizing	0.988	D	0.553	neutral	None	None	None	None	N
D/Q	0.3653	ambiguous	0.3222	benign	-0.414	Destabilizing	0.952	D	0.493	neutral	None	None	None	None	N
D/R	0.4736	ambiguous	0.4121	ambiguous	0.335	Stabilizing	0.976	D	0.57	neutral	None	None	None	None	N
D/S	0.1728	likely_benign	0.1517	benign	-0.691	Destabilizing	0.919	D	0.544	neutral	None	None	None	None	N
D/T	0.2297	likely_benign	0.2051	benign	-0.434	Destabilizing	0.919	D	0.528	neutral	None	None	None	None	N
D/V	0.1485	likely_benign	0.1411	benign	0.165	Stabilizing	0.984	D	0.639	neutral	N	0.458673642	None	None	N
D/W	0.8789	likely_pathogenic	0.8493	pathogenic	0.39	Stabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
D/Y	0.216	likely_benign	0.1931	benign	0.41	Stabilizing	0.995	D	0.674	neutral	N	0.506064944	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.