TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7068	21427;21428;21429	chr2:178724057;178724056;178724055	chr2:179588784;179588783;179588782
N2AB	6751	20476;20477;20478	chr2:178724057;178724056;178724055	chr2:179588784;179588783;179588782
N2A	5824	17695;17696;17697	chr2:178724057;178724056;178724055	chr2:179588784;179588783;179588782
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-55
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4265
• 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
A/T	None	None	0.006	N	0.234	0.087	0.216624796971	gnomAD-4.0.0	1.59209E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85956E-06	0	0
A/V	rs2078909515	None	0.193	N	0.371	0.165	0.43126412278	gnomAD-4.0.0	1.59209E-06	None	None	None	None	I	None	0	2.28906E-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
A/C	0.4372	ambiguous	0.4321	ambiguous	-0.796	Destabilizing	0.944	D	0.372	neutral	None	None	None	None	I
A/D	0.2807	likely_benign	0.2658	benign	-0.397	Destabilizing	0.324	N	0.404	neutral	N	0.486497748	None	None	I
A/E	0.2377	likely_benign	0.2389	benign	-0.507	Destabilizing	0.241	N	0.368	neutral	None	None	None	None	I
A/F	0.1996	likely_benign	0.1833	benign	-0.854	Destabilizing	0.818	D	0.414	neutral	None	None	None	None	I
A/G	0.1464	likely_benign	0.1449	benign	-0.619	Destabilizing	0.09	N	0.416	neutral	N	0.518706167	None	None	I
A/H	0.3848	ambiguous	0.3698	ambiguous	-0.685	Destabilizing	0.944	D	0.397	neutral	None	None	None	None	I
A/I	0.194	likely_benign	0.1792	benign	-0.267	Destabilizing	0.69	D	0.377	neutral	None	None	None	None	I
A/K	0.4291	ambiguous	0.4306	ambiguous	-0.818	Destabilizing	0.241	N	0.384	neutral	None	None	None	None	I
A/L	0.1391	likely_benign	0.1371	benign	-0.267	Destabilizing	0.241	N	0.372	neutral	None	None	None	None	I
A/M	0.1811	likely_benign	0.1683	benign	-0.29	Destabilizing	0.981	D	0.344	neutral	None	None	None	None	I
A/N	0.2442	likely_benign	0.2342	benign	-0.468	Destabilizing	0.527	D	0.42	neutral	None	None	None	None	I
A/P	0.7593	likely_pathogenic	0.8299	pathogenic	-0.297	Destabilizing	0.001	N	0.223	neutral	N	0.518879526	None	None	I
A/Q	0.3092	likely_benign	0.3065	benign	-0.687	Destabilizing	0.69	D	0.393	neutral	None	None	None	None	I
A/R	0.3419	ambiguous	0.3363	benign	-0.416	Destabilizing	0.69	D	0.387	neutral	None	None	None	None	I
A/S	0.0744	likely_benign	0.0719	benign	-0.784	Destabilizing	0.001	N	0.09	neutral	N	0.392912797	None	None	I
A/T	0.0764	likely_benign	0.0717	benign	-0.798	Destabilizing	0.006	N	0.234	neutral	N	0.443090901	None	None	I
A/V	0.1108	likely_benign	0.1041	benign	-0.297	Destabilizing	0.193	N	0.371	neutral	N	0.493578436	None	None	I
A/W	0.5299	ambiguous	0.5034	ambiguous	-1.059	Destabilizing	0.981	D	0.573	neutral	None	None	None	None	I
A/Y	0.3337	likely_benign	0.3097	benign	-0.685	Destabilizing	0.818	D	0.416	neutral	None	None	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.