TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21711	65356;65357;65358	chr2:178584420;178584419;178584418	chr2:179449147;179449146;179449145
N2AB	20070	60433;60434;60435	chr2:178584420;178584419;178584418	chr2:179449147;179449146;179449145
N2A	19143	57652;57653;57654	chr2:178584420;178584419;178584418	chr2:179449147;179449146;179449145
N2B	12646	38161;38162;38163	chr2:178584420;178584419;178584418	chr2:179449147;179449146;179449145
Novex-1	12771	38536;38537;38538	chr2:178584420;178584419;178584418	chr2:179449147;179449146;179449145
Novex-2	12838	38737;38738;38739	chr2:178584420;178584419;178584418	chr2:179449147;179449146;179449145
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: Fn3-45
• Domain position: 53
• Structural Position: 70
• Q(SASA): 1.0174
• 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
D/A	None	None	0.978	N	0.49	0.406	0.404733080969	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
D/A	0.3271	likely_benign	0.2752	benign	0.043	Stabilizing	0.978	D	0.49	neutral	N	0.487579892	None	None	I
D/C	0.8266	likely_pathogenic	0.7886	pathogenic	0.069	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	I
D/E	0.188	likely_benign	0.162	benign	-0.197	Destabilizing	0.198	N	0.261	neutral	N	0.408849749	None	None	I
D/F	0.8651	likely_pathogenic	0.8336	pathogenic	-0.132	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	I
D/G	0.296	likely_benign	0.2665	benign	-0.061	Destabilizing	0.989	D	0.547	neutral	N	0.488273325	None	None	I
D/H	0.4765	ambiguous	0.4099	ambiguous	0.354	Stabilizing	1.0	D	0.502	neutral	N	0.507032444	None	None	I
D/I	0.6635	likely_pathogenic	0.6142	pathogenic	0.245	Stabilizing	0.999	D	0.597	neutral	None	None	None	None	I
D/K	0.5405	ambiguous	0.4821	ambiguous	0.507	Stabilizing	0.983	D	0.541	neutral	None	None	None	None	I
D/L	0.6482	likely_pathogenic	0.5967	pathogenic	0.245	Stabilizing	0.998	D	0.602	neutral	None	None	None	None	I
D/M	0.8201	likely_pathogenic	0.7733	pathogenic	0.16	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	I
D/N	0.1637	likely_benign	0.1372	benign	0.399	Stabilizing	0.989	D	0.502	neutral	N	0.486387813	None	None	I
D/P	0.7458	likely_pathogenic	0.6946	pathogenic	0.197	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	I
D/Q	0.4854	ambiguous	0.4235	ambiguous	0.382	Stabilizing	0.995	D	0.5	neutral	None	None	None	None	I
D/R	0.5875	likely_pathogenic	0.5201	ambiguous	0.648	Stabilizing	0.995	D	0.541	neutral	None	None	None	None	I
D/S	0.2134	likely_benign	0.1846	benign	0.276	Stabilizing	0.983	D	0.513	neutral	None	None	None	None	I
D/T	0.3866	ambiguous	0.3367	benign	0.357	Stabilizing	0.998	D	0.471	neutral	None	None	None	None	I
D/V	0.4422	ambiguous	0.3972	ambiguous	0.197	Stabilizing	0.997	D	0.597	neutral	N	0.501797196	None	None	I
D/W	0.9574	likely_pathogenic	0.9473	pathogenic	-0.118	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
D/Y	0.4778	ambiguous	0.4476	ambiguous	0.088	Stabilizing	1.0	D	0.579	neutral	N	0.510648752	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.