TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4834	14725;14726;14727	chr2:178735946;178735945;178735944	chr2:179600673;179600672;179600671
N2AB	4517	13774;13775;13776	chr2:178735946;178735945;178735944	chr2:179600673;179600672;179600671
N2A	3590	10993;10994;10995	chr2:178735946;178735945;178735944	chr2:179600673;179600672;179600671
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: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-31
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4549
• 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/S	rs746792103	-0.113	0.565	N	0.477	0.077	0.17948927462	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
A/S	rs746792103	-0.113	0.565	N	0.477	0.077	0.17948927462	gnomAD-4.0.0	1.36839E-06	None	None	None	None	N	None	0	0	None	0	2.52029E-05	None	0	0	8.9946E-07	0	0
A/T	None	None	0.008	N	0.211	0.063	0.15556083564	gnomAD-4.0.0	6.84197E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-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	0.4942	ambiguous	0.4345	ambiguous	-0.78	Destabilizing	0.989	D	0.531	neutral	None	None	None	None	N
A/D	0.2221	likely_benign	0.1857	benign	-0.337	Destabilizing	0.024	N	0.346	neutral	None	None	None	None	N
A/E	0.1832	likely_benign	0.1624	benign	-0.48	Destabilizing	0.565	D	0.524	neutral	N	0.486096908	None	None	N
A/F	0.2326	likely_benign	0.2007	benign	-0.834	Destabilizing	0.923	D	0.692	prob.neutral	None	None	None	None	N
A/G	0.1538	likely_benign	0.1374	benign	-0.339	Destabilizing	0.722	D	0.451	neutral	D	0.575650028	None	None	N
A/H	0.3956	ambiguous	0.3402	ambiguous	-0.367	Destabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	N
A/I	0.1487	likely_benign	0.1253	benign	-0.295	Destabilizing	0.372	N	0.517	neutral	None	None	None	None	N
A/K	0.3194	likely_benign	0.2711	benign	-0.637	Destabilizing	0.923	D	0.523	neutral	None	None	None	None	N
A/L	0.1324	likely_benign	0.1152	benign	-0.295	Destabilizing	0.633	D	0.5	neutral	None	None	None	None	N
A/M	0.1954	likely_benign	0.1631	benign	-0.402	Destabilizing	0.979	D	0.621	neutral	None	None	None	None	N
A/N	0.2009	likely_benign	0.1699	benign	-0.325	Destabilizing	0.923	D	0.664	neutral	None	None	None	None	N
A/P	0.116	likely_benign	0.1034	benign	-0.254	Destabilizing	0.949	D	0.603	neutral	N	0.438733132	None	None	N
A/Q	0.2598	likely_benign	0.2276	benign	-0.576	Destabilizing	0.961	D	0.621	neutral	None	None	None	None	N
A/R	0.2914	likely_benign	0.2605	benign	-0.203	Destabilizing	0.923	D	0.617	neutral	None	None	None	None	N
A/S	0.0889	likely_benign	0.0845	benign	-0.554	Destabilizing	0.565	D	0.477	neutral	N	0.504404477	None	None	N
A/T	0.0805	likely_benign	0.0744	benign	-0.611	Destabilizing	0.008	N	0.211	neutral	N	0.498425312	None	None	N
A/V	0.0908	likely_benign	0.0825	benign	-0.254	Destabilizing	0.008	N	0.279	neutral	N	0.509093356	None	None	N
A/W	0.66	likely_pathogenic	0.5815	pathogenic	-0.989	Destabilizing	0.996	D	0.744	deleterious	None	None	None	None	N
A/Y	0.3957	ambiguous	0.3244	benign	-0.633	Destabilizing	0.961	D	0.686	prob.neutral	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.