TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27484	82675;82676;82677	chr2:178563682;178563681;178563680	chr2:179428409;179428408;179428407
N2AB	25843	77752;77753;77754	chr2:178563682;178563681;178563680	chr2:179428409;179428408;179428407
N2A	24916	74971;74972;74973	chr2:178563682;178563681;178563680	chr2:179428409;179428408;179428407
N2B	18419	55480;55481;55482	chr2:178563682;178563681;178563680	chr2:179428409;179428408;179428407
Novex-1	18544	55855;55856;55857	chr2:178563682;178563681;178563680	chr2:179428409;179428408;179428407
Novex-2	18611	56056;56057;56058	chr2:178563682;178563681;178563680	chr2:179428409;179428408;179428407
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: Fn3-88
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.6199
• 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	rs1444267232	0.264	0.032	N	0.243	0.202	0.159798565429	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
D/N	rs1444267232	0.264	0.032	N	0.243	0.202	0.159798565429	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	2.28634E-05	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	0.6069	likely_pathogenic	0.5285	ambiguous	-0.427	Destabilizing	0.698	D	0.605	neutral	N	0.499312089	None	None	N
D/C	0.9075	likely_pathogenic	0.8809	pathogenic	0.204	Stabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
D/E	0.3619	ambiguous	0.2931	benign	-0.491	Destabilizing	0.014	N	0.226	neutral	N	0.473370247	None	None	N
D/F	0.8606	likely_pathogenic	0.8361	pathogenic	-0.726	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
D/G	0.452	ambiguous	0.3861	ambiguous	-0.62	Destabilizing	0.698	D	0.578	neutral	N	0.46736954	None	None	N
D/H	0.7023	likely_pathogenic	0.6348	pathogenic	-0.929	Destabilizing	0.992	D	0.647	neutral	D	0.523946124	None	None	N
D/I	0.833	likely_pathogenic	0.7967	pathogenic	0.036	Stabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
D/K	0.8566	likely_pathogenic	0.8113	pathogenic	0.29	Stabilizing	0.754	D	0.615	neutral	None	None	None	None	N
D/L	0.8319	likely_pathogenic	0.7926	pathogenic	0.036	Stabilizing	0.956	D	0.741	deleterious	None	None	None	None	N
D/M	0.8977	likely_pathogenic	0.868	pathogenic	0.489	Stabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
D/N	0.1829	likely_benign	0.1622	benign	0.081	Stabilizing	0.032	N	0.243	neutral	N	0.477440256	None	None	N
D/P	0.9917	likely_pathogenic	0.9891	pathogenic	-0.097	Destabilizing	0.978	D	0.672	neutral	None	None	None	None	N
D/Q	0.7693	likely_pathogenic	0.6977	pathogenic	0.068	Stabilizing	0.915	D	0.647	neutral	None	None	None	None	N
D/R	0.875	likely_pathogenic	0.8422	pathogenic	0.174	Stabilizing	0.956	D	0.724	prob.delet.	None	None	None	None	N
D/S	0.3822	ambiguous	0.328	benign	-0.043	Destabilizing	0.754	D	0.519	neutral	None	None	None	None	N
D/T	0.5267	ambiguous	0.4536	ambiguous	0.111	Stabilizing	0.956	D	0.624	neutral	None	None	None	None	N
D/V	0.6689	likely_pathogenic	0.6121	pathogenic	-0.097	Destabilizing	0.942	D	0.74	deleterious	D	0.522278189	None	None	N
D/W	0.975	likely_pathogenic	0.969	pathogenic	-0.679	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
D/Y	0.4762	ambiguous	0.4289	ambiguous	-0.5	Destabilizing	0.997	D	0.733	prob.delet.	N	0.510668394	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.