TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5949	18070;18071;18072	chr2:178730688;178730687;178730686	chr2:179595415;179595414;179595413
N2AB	5632	17119;17120;17121	chr2:178730688;178730687;178730686	chr2:179595415;179595414;179595413
N2A	4705	14338;14339;14340	chr2:178730688;178730687;178730686	chr2:179595415;179595414;179595413
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-43
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4677
• 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
S/G	rs368275231	-0.598	0.625	N	0.416	0.33	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
S/G	rs368275231	-0.598	0.625	N	0.416	0.33	None	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85889E-06	0	0
S/N	rs1578154475	None	0.051	N	0.183	0.121	0.215869574891	gnomAD-4.0.0	1.36855E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99539E-07	0	1.65673E-05

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
S/A	0.0917	likely_benign	0.0843	benign	-0.679	Destabilizing	0.525	D	0.337	neutral	None	None	None	None	N
S/C	0.1996	likely_benign	0.1596	benign	-0.485	Destabilizing	0.997	D	0.495	neutral	D	0.522945386	None	None	N
S/D	0.3372	likely_benign	0.3481	ambiguous	0.304	Stabilizing	0.728	D	0.375	neutral	None	None	None	None	N
S/E	0.482	ambiguous	0.4821	ambiguous	0.292	Stabilizing	0.842	D	0.374	neutral	None	None	None	None	N
S/F	0.1982	likely_benign	0.1756	benign	-1.047	Destabilizing	0.949	D	0.591	neutral	None	None	None	None	N
S/G	0.1322	likely_benign	0.1371	benign	-0.891	Destabilizing	0.625	D	0.416	neutral	N	0.501193826	None	None	N
S/H	0.2774	likely_benign	0.2553	benign	-1.288	Destabilizing	0.974	D	0.523	neutral	None	None	None	None	N
S/I	0.1844	likely_benign	0.1681	benign	-0.232	Destabilizing	0.669	D	0.543	neutral	N	0.488685432	None	None	N
S/K	0.5827	likely_pathogenic	0.5638	ambiguous	-0.444	Destabilizing	0.842	D	0.37	neutral	None	None	None	None	N
S/L	0.1228	likely_benign	0.1078	benign	-0.232	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
S/M	0.2232	likely_benign	0.1892	benign	-0.153	Destabilizing	0.949	D	0.527	neutral	None	None	None	None	N
S/N	0.1224	likely_benign	0.1229	benign	-0.404	Destabilizing	0.051	N	0.183	neutral	N	0.503488786	None	None	N
S/P	0.8625	likely_pathogenic	0.8936	pathogenic	-0.349	Destabilizing	0.974	D	0.557	neutral	None	None	None	None	N
S/Q	0.442	ambiguous	0.4188	ambiguous	-0.486	Destabilizing	0.974	D	0.479	neutral	None	None	None	None	N
S/R	0.4617	ambiguous	0.4743	ambiguous	-0.382	Destabilizing	0.966	D	0.547	neutral	N	0.48392159	None	None	N
S/T	0.0708	likely_benign	0.0663	benign	-0.462	Destabilizing	0.022	N	0.123	neutral	N	0.4404961	None	None	N
S/V	0.1967	likely_benign	0.1697	benign	-0.349	Destabilizing	0.728	D	0.502	neutral	None	None	None	None	N
S/W	0.4037	ambiguous	0.3937	ambiguous	-1.037	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
S/Y	0.1821	likely_benign	0.172	benign	-0.744	Destabilizing	0.991	D	0.583	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.