TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28735	86428;86429;86430	chr2:178559929;178559928;178559927	chr2:179424656;179424655;179424654
N2AB	27094	81505;81506;81507	chr2:178559929;178559928;178559927	chr2:179424656;179424655;179424654
N2A	26167	78724;78725;78726	chr2:178559929;178559928;178559927	chr2:179424656;179424655;179424654
N2B	19670	59233;59234;59235	chr2:178559929;178559928;178559927	chr2:179424656;179424655;179424654
Novex-1	19795	59608;59609;59610	chr2:178559929;178559928;178559927	chr2:179424656;179424655;179424654
Novex-2	19862	59809;59810;59811	chr2:178559929;178559928;178559927	chr2:179424656;179424655;179424654
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-97
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.701
• 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/E	None	None	0.006	N	0.099	0.038	0.0806252709748	gnomAD-4.0.0	6.84249E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99476E-07	0	0
D/N	rs1703015531	None	0.822	N	0.574	0.217	0.215109475489	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1703015531	None	0.822	N	0.574	0.217	0.215109475489	gnomAD-4.0.0	6.57108E-06	None	None	None	None	I	None	2.4122E-05	0	None	0	0	None	0	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	0.1958	likely_benign	0.1822	benign	-0.303	Destabilizing	0.822	D	0.493	neutral	N	0.459393213	None	None	I
D/C	0.6649	likely_pathogenic	0.6761	pathogenic	0.066	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	I
D/E	0.1129	likely_benign	0.1148	benign	-0.369	Destabilizing	0.006	N	0.099	neutral	N	0.376371971	None	None	I
D/F	0.5641	likely_pathogenic	0.5596	ambiguous	-0.29	Destabilizing	0.993	D	0.616	neutral	None	None	None	None	I
D/G	0.2968	likely_benign	0.2874	benign	-0.497	Destabilizing	0.822	D	0.511	neutral	N	0.510763396	None	None	I
D/H	0.4029	ambiguous	0.3814	ambiguous	-0.165	Destabilizing	0.97	D	0.577	neutral	D	0.523020617	None	None	I
D/I	0.3149	likely_benign	0.2906	benign	0.159	Stabilizing	0.978	D	0.593	neutral	None	None	None	None	I
D/K	0.4276	ambiguous	0.4073	ambiguous	0.292	Stabilizing	0.754	D	0.47	neutral	None	None	None	None	I
D/L	0.3402	ambiguous	0.306	benign	0.159	Stabilizing	0.956	D	0.52	neutral	None	None	None	None	I
D/M	0.5357	ambiguous	0.5227	ambiguous	0.333	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	I
D/N	0.1559	likely_benign	0.1487	benign	0.033	Stabilizing	0.822	D	0.574	neutral	N	0.485753095	None	None	I
D/P	0.5653	likely_pathogenic	0.5582	ambiguous	0.027	Stabilizing	0.978	D	0.571	neutral	None	None	None	None	I
D/Q	0.3506	ambiguous	0.333	benign	0.046	Stabilizing	0.754	D	0.522	neutral	None	None	None	None	I
D/R	0.5052	ambiguous	0.4879	ambiguous	0.438	Stabilizing	0.043	N	0.339	neutral	None	None	None	None	I
D/S	0.1713	likely_benign	0.1596	benign	-0.081	Destabilizing	0.86	D	0.465	neutral	None	None	None	None	I
D/T	0.2907	likely_benign	0.2754	benign	0.066	Stabilizing	0.86	D	0.562	neutral	None	None	None	None	I
D/V	0.2	likely_benign	0.1839	benign	0.027	Stabilizing	0.97	D	0.539	neutral	N	0.463761669	None	None	I
D/W	0.8956	likely_pathogenic	0.905	pathogenic	-0.167	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	I
D/Y	0.2742	likely_benign	0.2657	benign	-0.052	Destabilizing	0.99	D	0.615	neutral	N	0.469976433	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.