TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5618	17077;17078;17079	chr2:178732117;178732116;178732115	chr2:179596844;179596843;179596842
N2AB	5301	16126;16127;16128	chr2:178732117;178732116;178732115	chr2:179596844;179596843;179596842
N2A	4374	13345;13346;13347	chr2:178732117;178732116;178732115	chr2:179596844;179596843;179596842
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-39
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.108
• 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/V	rs774980198	-0.332	1.0	N	0.649	0.521	0.615473259424	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.22767E-04	None	0	None	0	0	0
A/V	rs774980198	-0.332	1.0	N	0.649	0.521	0.615473259424	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92901E-04	None	0	0	0	0	0
A/V	rs774980198	-0.332	1.0	N	0.649	0.521	0.615473259424	gnomAD-4.0.0	6.19878E-06	None	None	None	None	N	None	0	0	None	0	2.22846E-04	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	0.8511	likely_pathogenic	0.8636	pathogenic	-1.944	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
A/D	0.9928	likely_pathogenic	0.99	pathogenic	-3.077	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.655948641	None	None	N
A/E	0.9833	likely_pathogenic	0.9784	pathogenic	-2.926	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/F	0.904	likely_pathogenic	0.8971	pathogenic	-0.884	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
A/G	0.36	ambiguous	0.3526	ambiguous	-1.755	Destabilizing	1.0	D	0.576	neutral	D	0.58705646	None	None	N
A/H	0.9941	likely_pathogenic	0.9929	pathogenic	-1.763	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
A/I	0.5028	ambiguous	0.4681	ambiguous	-0.343	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
A/K	0.9949	likely_pathogenic	0.9933	pathogenic	-1.474	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/L	0.5421	ambiguous	0.5177	ambiguous	-0.343	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
A/M	0.6984	likely_pathogenic	0.6902	pathogenic	-0.817	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/N	0.9806	likely_pathogenic	0.977	pathogenic	-1.848	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/P	0.9892	likely_pathogenic	0.9864	pathogenic	-0.647	Destabilizing	1.0	D	0.881	deleterious	D	0.630208725	None	None	N
A/Q	0.9804	likely_pathogenic	0.9761	pathogenic	-1.781	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/R	0.9855	likely_pathogenic	0.9811	pathogenic	-1.354	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/S	0.4174	ambiguous	0.4058	ambiguous	-2.174	Highly Destabilizing	1.0	D	0.575	neutral	D	0.607052981	None	None	N
A/T	0.4998	ambiguous	0.4736	ambiguous	-1.92	Destabilizing	1.0	D	0.782	deleterious	D	0.629603312	None	None	N
A/V	0.2442	likely_benign	0.2178	benign	-0.647	Destabilizing	1.0	D	0.649	neutral	N	0.511076237	None	None	N
A/W	0.9948	likely_pathogenic	0.994	pathogenic	-1.493	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/Y	0.9731	likely_pathogenic	0.971	pathogenic	-1.068	Destabilizing	1.0	D	0.898	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.