TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8720	26383;26384;26385	chr2:178715028;178715027;178715026	chr2:179579755;179579754;179579753
N2AB	8403	25432;25433;25434	chr2:178715028;178715027;178715026	chr2:179579755;179579754;179579753
N2A	7476	22651;22652;22653	chr2:178715028;178715027;178715026	chr2:179579755;179579754;179579753
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-72
• Domain position: 78
• Structural Position: 162
• Q(SASA): 1.0493
• 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/N	rs980079508	0.565	0.008	N	0.269	0.198	0.288727942641	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
D/N	rs980079508	0.565	0.008	N	0.269	0.198	0.288727942641	gnomAD-4.0.0	2.05364E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69958E-06	0	0
D/Y	rs980079508	None	0.991	N	0.342	0.344	0.53371040847	gnomAD-4.0.0	2.73818E-06	None	None	None	None	I	None	8.97076E-05	0	None	0	0	None	0	0	8.99858E-07	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	0.1509	likely_benign	0.1728	benign	0.051	Stabilizing	0.227	N	0.371	neutral	N	0.473701809	None	None	I
D/C	0.6493	likely_pathogenic	0.6869	pathogenic	-0.058	Destabilizing	0.978	D	0.329	neutral	None	None	None	None	I
D/E	0.1095	likely_benign	0.1116	benign	-0.395	Destabilizing	None	N	0.19	neutral	N	0.419365892	None	None	I
D/F	0.5595	ambiguous	0.6079	pathogenic	-0.12	Destabilizing	0.98	D	0.343	neutral	None	None	None	None	I
D/G	0.2078	likely_benign	0.2548	benign	-0.041	Destabilizing	0.298	N	0.365	neutral	N	0.467391912	None	None	I
D/H	0.2812	likely_benign	0.3259	benign	0.447	Stabilizing	0.931	D	0.343	neutral	N	0.519090169	None	None	I
D/I	0.305	likely_benign	0.3293	benign	0.223	Stabilizing	0.772	D	0.363	neutral	None	None	None	None	I
D/K	0.3605	ambiguous	0.4263	ambiguous	0.466	Stabilizing	0.772	D	0.375	neutral	None	None	None	None	I
D/L	0.3503	ambiguous	0.393	ambiguous	0.223	Stabilizing	0.772	D	0.394	neutral	None	None	None	None	I
D/M	0.5234	ambiguous	0.5598	ambiguous	0.068	Stabilizing	0.985	D	0.321	neutral	None	None	None	None	I
D/N	0.1135	likely_benign	0.1238	benign	0.281	Stabilizing	0.008	N	0.269	neutral	N	0.462004735	None	None	I
D/P	0.7046	likely_pathogenic	0.7504	pathogenic	0.184	Stabilizing	0.487	N	0.357	neutral	None	None	None	None	I
D/Q	0.3061	likely_benign	0.3476	ambiguous	0.262	Stabilizing	0.559	D	0.287	neutral	None	None	None	None	I
D/R	0.395	ambiguous	0.4659	ambiguous	0.634	Stabilizing	0.96	D	0.375	neutral	None	None	None	None	I
D/S	0.1264	likely_benign	0.1416	benign	0.198	Stabilizing	0.03	N	0.157	neutral	None	None	None	None	I
D/T	0.2176	likely_benign	0.2449	benign	0.273	Stabilizing	0.296	N	0.379	neutral	None	None	None	None	I
D/V	0.188	likely_benign	0.2058	benign	0.184	Stabilizing	0.012	N	0.315	neutral	N	0.491346208	None	None	I
D/W	0.8712	likely_pathogenic	0.8922	pathogenic	-0.109	Destabilizing	0.998	D	0.436	neutral	None	None	None	None	I
D/Y	0.2445	likely_benign	0.2744	benign	0.098	Stabilizing	0.991	D	0.342	neutral	N	0.485225484	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.