TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7378	22357;22358;22359	chr2:178722767;178722766;178722765	chr2:179587494;179587493;179587492
N2AB	7061	21406;21407;21408	chr2:178722767;178722766;178722765	chr2:179587494;179587493;179587492
N2A	6134	18625;18626;18627	chr2:178722767;178722766;178722765	chr2:179587494;179587493;179587492
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-58
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1034
• 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
A/T	rs879099986	None	1.0	N	0.66	0.273	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs879099986	None	1.0	N	0.66	0.273	None	gnomAD-4.0.0	9.91838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.27168E-05	1.09832E-05	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
A/C	0.8246	likely_pathogenic	0.8171	pathogenic	-0.967	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/D	0.9852	likely_pathogenic	0.993	pathogenic	-2.369	Highly Destabilizing	1.0	D	0.747	deleterious	N	0.469961708	None	None	N
A/E	0.9688	likely_pathogenic	0.9871	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/F	0.8678	likely_pathogenic	0.9207	pathogenic	-0.56	Destabilizing	0.946	D	0.691	prob.neutral	None	None	None	None	N
A/G	0.3581	ambiguous	0.4073	ambiguous	-1.427	Destabilizing	0.979	D	0.635	neutral	N	0.455285754	None	None	N
A/H	0.9685	likely_pathogenic	0.9794	pathogenic	-2.039	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
A/I	0.8256	likely_pathogenic	0.9011	pathogenic	0.392	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
A/K	0.9896	likely_pathogenic	0.9956	pathogenic	-0.977	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
A/L	0.6765	likely_pathogenic	0.7608	pathogenic	0.392	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
A/M	0.7724	likely_pathogenic	0.8473	pathogenic	0.091	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
A/N	0.9584	likely_pathogenic	0.975	pathogenic	-1.352	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/P	0.9806	likely_pathogenic	0.9894	pathogenic	-0.009	Destabilizing	1.0	D	0.741	deleterious	N	0.467239457	None	None	N
A/Q	0.9456	likely_pathogenic	0.9708	pathogenic	-1.099	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/R	0.97	likely_pathogenic	0.9838	pathogenic	-1.199	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/S	0.3028	likely_benign	0.3423	ambiguous	-1.716	Destabilizing	0.99	D	0.459	neutral	N	0.473580726	None	None	N
A/T	0.4959	ambiguous	0.5867	pathogenic	-1.372	Destabilizing	1.0	D	0.66	neutral	N	0.502730197	None	None	N
A/V	0.5347	ambiguous	0.6561	pathogenic	-0.009	Destabilizing	0.999	D	0.655	neutral	N	0.453437162	None	None	N
A/W	0.9882	likely_pathogenic	0.9929	pathogenic	-1.45	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
A/Y	0.9455	likely_pathogenic	0.9705	pathogenic	-0.852	Destabilizing	1.0	D	0.75	deleterious	None	None	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.