TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17426	52501;52502;52503	chr2:178608735;178608734;178608733	chr2:179473462;179473461;179473460
N2AB	15785	47578;47579;47580	chr2:178608735;178608734;178608733	chr2:179473462;179473461;179473460
N2A	14858	44797;44798;44799	chr2:178608735;178608734;178608733	chr2:179473462;179473461;179473460
N2B	8361	25306;25307;25308	chr2:178608735;178608734;178608733	chr2:179473462;179473461;179473460
Novex-1	8486	25681;25682;25683	chr2:178608735;178608734;178608733	chr2:179473462;179473461;179473460
Novex-2	8553	25882;25883;25884	chr2:178608735;178608734;178608733	chr2:179473462;179473461;179473460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-14
• Domain position: 58
• Structural Position: 83
• Q(SASA): 0.5488
• Predicted PPI site: I

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
R/T	None	None	0.967	N	0.605	0.336	0.32980341726	gnomAD-4.0.0	1.59378E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.862E-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
R/A	0.7246	likely_pathogenic	0.7872	pathogenic	0.088	Stabilizing	0.845	D	0.569	neutral	None	None	None	None	I
R/C	0.3645	ambiguous	0.3903	ambiguous	0.087	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	I
R/D	0.9022	likely_pathogenic	0.9309	pathogenic	0.037	Stabilizing	0.975	D	0.614	neutral	None	None	None	None	I
R/E	0.6869	likely_pathogenic	0.7483	pathogenic	0.121	Stabilizing	0.845	D	0.553	neutral	None	None	None	None	I
R/F	0.8293	likely_pathogenic	0.8669	pathogenic	-0.005	Destabilizing	0.996	D	0.629	neutral	None	None	None	None	I
R/G	0.5631	ambiguous	0.6293	pathogenic	-0.146	Destabilizing	0.892	D	0.524	neutral	N	0.465743182	None	None	I
R/H	0.2216	likely_benign	0.2431	benign	-0.749	Destabilizing	0.987	D	0.64	neutral	None	None	None	None	I
R/I	0.5701	likely_pathogenic	0.6273	pathogenic	0.68	Stabilizing	0.983	D	0.639	neutral	N	0.483771582	None	None	I
R/K	0.1779	likely_benign	0.1911	benign	0.099	Stabilizing	0.025	N	0.212	neutral	N	0.377489479	None	None	I
R/L	0.4682	ambiguous	0.5126	ambiguous	0.68	Stabilizing	0.916	D	0.524	neutral	None	None	None	None	I
R/M	0.6033	likely_pathogenic	0.6686	pathogenic	0.182	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	I
R/N	0.8315	likely_pathogenic	0.8797	pathogenic	0.413	Stabilizing	0.975	D	0.595	neutral	None	None	None	None	I
R/P	0.7095	likely_pathogenic	0.7769	pathogenic	0.504	Stabilizing	0.987	D	0.624	neutral	None	None	None	None	I
R/Q	0.1923	likely_benign	0.2096	benign	0.327	Stabilizing	0.975	D	0.596	neutral	None	None	None	None	I
R/S	0.7698	likely_pathogenic	0.8231	pathogenic	0.057	Stabilizing	0.892	D	0.603	neutral	N	0.442383533	None	None	I
R/T	0.5522	ambiguous	0.6378	pathogenic	0.289	Stabilizing	0.967	D	0.605	neutral	N	0.43534013	None	None	I
R/V	0.6615	likely_pathogenic	0.7154	pathogenic	0.504	Stabilizing	0.975	D	0.642	neutral	None	None	None	None	I
R/W	0.3635	ambiguous	0.3954	ambiguous	-0.024	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
R/Y	0.6772	likely_pathogenic	0.7282	pathogenic	0.374	Stabilizing	0.996	D	0.627	neutral	None	None	None	None	I

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.