TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8405	25438;25439;25440	chr2:178717661;178717660;178717659	chr2:179582388;179582387;179582386
N2AB	8088	24487;24488;24489	chr2:178717661;178717660;178717659	chr2:179582388;179582387;179582386
N2A	7161	21706;21707;21708	chr2:178717661;178717660;178717659	chr2:179582388;179582387;179582386
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-69
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.2572
• 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
N/K	rs371923232	-0.094	0.649	N	0.205	0.141	0.168933306366	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
N/K	rs371923232	-0.094	0.649	N	0.205	0.141	0.168933306366	gnomAD-4.0.0	1.11566E-05	None	None	None	None	N	None	1.33483E-05	0	None	0	0	None	0	0	1.35637E-05	0	1.60154E-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
N/A	0.366	ambiguous	0.3779	ambiguous	-0.63	Destabilizing	0.705	D	0.365	neutral	None	None	None	None	N
N/C	0.4937	ambiguous	0.4931	ambiguous	0.299	Stabilizing	1.0	D	0.523	neutral	None	None	None	None	N
N/D	0.2421	likely_benign	0.2531	benign	-0.311	Destabilizing	0.034	N	0.172	neutral	N	0.485804315	None	None	N
N/E	0.6298	likely_pathogenic	0.6532	pathogenic	-0.249	Destabilizing	0.396	N	0.25	neutral	None	None	None	None	N
N/F	0.6358	likely_pathogenic	0.6285	pathogenic	-0.459	Destabilizing	1.0	D	0.487	neutral	None	None	None	None	N
N/G	0.4121	ambiguous	0.419	ambiguous	-0.949	Destabilizing	0.981	D	0.292	neutral	None	None	None	None	N
N/H	0.1424	likely_benign	0.1493	benign	-0.89	Destabilizing	0.999	D	0.399	neutral	N	0.5082571	None	None	N
N/I	0.3925	ambiguous	0.3863	ambiguous	0.166	Stabilizing	0.997	D	0.479	neutral	N	0.485136579	None	None	N
N/K	0.4957	ambiguous	0.5291	ambiguous	-0.308	Destabilizing	0.649	D	0.205	neutral	N	0.493036932	None	None	N
N/L	0.3431	ambiguous	0.3313	benign	0.166	Stabilizing	0.993	D	0.471	neutral	None	None	None	None	N
N/M	0.5157	ambiguous	0.5102	ambiguous	0.625	Stabilizing	1.0	D	0.423	neutral	None	None	None	None	N
N/P	0.811	likely_pathogenic	0.8259	pathogenic	-0.069	Destabilizing	0.991	D	0.432	neutral	None	None	None	None	N
N/Q	0.4877	ambiguous	0.5019	ambiguous	-0.692	Destabilizing	0.996	D	0.357	neutral	None	None	None	None	N
N/R	0.4522	ambiguous	0.4889	ambiguous	-0.404	Destabilizing	0.989	D	0.357	neutral	None	None	None	None	N
N/S	0.1113	likely_benign	0.1137	benign	-0.671	Destabilizing	0.304	N	0.212	neutral	N	0.506928949	None	None	N
N/T	0.2439	likely_benign	0.2529	benign	-0.433	Destabilizing	0.896	D	0.306	neutral	N	0.515799148	None	None	N
N/V	0.3707	ambiguous	0.3608	ambiguous	-0.069	Destabilizing	0.976	D	0.481	neutral	None	None	None	None	N
N/W	0.8682	likely_pathogenic	0.8777	pathogenic	-0.319	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
N/Y	0.246	likely_benign	0.2543	benign	-0.122	Destabilizing	1.0	D	0.425	neutral	N	0.518186092	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.