TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5653	17182;17183;17184	chr2:178731918;178731917;178731916	chr2:179596645;179596644;179596643
N2AB	5336	16231;16232;16233	chr2:178731918;178731917;178731916	chr2:179596645;179596644;179596643
N2A	4409	13450;13451;13452	chr2:178731918;178731917;178731916	chr2:179596645;179596644;179596643
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-40
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3412
• 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
D/N	rs267599067	-0.846	1.0	N	0.565	0.31	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
D/N	rs267599067	-0.846	1.0	N	0.565	0.31	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs267599067	-0.846	1.0	N	0.565	0.31	None	gnomAD-4.0.0	9.91669E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.3247E-06	4.39309E-05	1.60118E-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
D/A	0.6242	likely_pathogenic	0.6321	pathogenic	-0.378	Destabilizing	0.989	D	0.522	neutral	N	0.487955533	None	None	N
D/C	0.9535	likely_pathogenic	0.9568	pathogenic	-0.227	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
D/E	0.4517	ambiguous	0.4863	ambiguous	-0.493	Destabilizing	0.543	D	0.248	neutral	N	0.473890158	None	None	N
D/F	0.9622	likely_pathogenic	0.9598	pathogenic	0.281	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
D/G	0.6492	likely_pathogenic	0.6513	pathogenic	-0.748	Destabilizing	0.994	D	0.535	neutral	N	0.471683229	None	None	N
D/H	0.7565	likely_pathogenic	0.7763	pathogenic	0.08	Stabilizing	1.0	D	0.651	neutral	N	0.472443697	None	None	N
D/I	0.9044	likely_pathogenic	0.9008	pathogenic	0.604	Stabilizing	0.995	D	0.706	prob.neutral	None	None	None	None	N
D/K	0.9002	likely_pathogenic	0.9099	pathogenic	-0.249	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
D/L	0.9092	likely_pathogenic	0.9079	pathogenic	0.604	Stabilizing	0.995	D	0.667	neutral	None	None	None	None	N
D/M	0.9608	likely_pathogenic	0.9626	pathogenic	0.887	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
D/N	0.2789	likely_benign	0.2956	benign	-0.846	Destabilizing	1.0	D	0.565	neutral	N	0.47129257	None	None	N
D/P	0.8808	likely_pathogenic	0.8768	pathogenic	0.303	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
D/Q	0.8246	likely_pathogenic	0.8454	pathogenic	-0.662	Destabilizing	0.998	D	0.618	neutral	None	None	None	None	N
D/R	0.8851	likely_pathogenic	0.8993	pathogenic	0.012	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
D/S	0.3966	ambiguous	0.4046	ambiguous	-1.071	Destabilizing	0.992	D	0.487	neutral	None	None	None	None	N
D/T	0.7	likely_pathogenic	0.6946	pathogenic	-0.757	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
D/V	0.7768	likely_pathogenic	0.7663	pathogenic	0.303	Stabilizing	0.733	D	0.427	neutral	N	0.492438633	None	None	N
D/W	0.988	likely_pathogenic	0.9886	pathogenic	0.508	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
D/Y	0.75	likely_pathogenic	0.7435	pathogenic	0.536	Stabilizing	1.0	D	0.763	deleterious	N	0.490547952	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.