TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19920	59983;59984;59985	chr2:178592146;178592145;178592144	chr2:179456873;179456872;179456871
N2AB	18279	55060;55061;55062	chr2:178592146;178592145;178592144	chr2:179456873;179456872;179456871
N2A	17352	52279;52280;52281	chr2:178592146;178592145;178592144	chr2:179456873;179456872;179456871
N2B	10855	32788;32789;32790	chr2:178592146;178592145;178592144	chr2:179456873;179456872;179456871
Novex-1	10980	33163;33164;33165	chr2:178592146;178592145;178592144	chr2:179456873;179456872;179456871
Novex-2	11047	33364;33365;33366	chr2:178592146;178592145;178592144	chr2:179456873;179456872;179456871
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: Fn3-32
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.6641
• 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	None	None	0.998	N	0.511	0.351	0.453679287548	gnomAD-4.0.0	1.59311E-06	None	None	None	None	N	None	0	0	None	0	2.79065E-05	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	0.458	ambiguous	0.4197	ambiguous	-0.908	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
A/D	0.2893	likely_benign	0.2559	benign	-0.553	Destabilizing	0.999	D	0.656	neutral	N	0.451021659	None	None	N
A/E	0.2856	likely_benign	0.2757	benign	-0.703	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
A/F	0.3471	ambiguous	0.3129	benign	-0.929	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
A/G	0.1344	likely_benign	0.1173	benign	-0.28	Destabilizing	0.996	D	0.433	neutral	N	0.393858867	None	None	N
A/H	0.4277	ambiguous	0.4145	ambiguous	-0.215	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
A/I	0.2524	likely_benign	0.2227	benign	-0.452	Destabilizing	1.0	D	0.59	neutral	None	None	None	None	N
A/K	0.4647	ambiguous	0.4443	ambiguous	-0.587	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
A/L	0.1684	likely_benign	0.1557	benign	-0.452	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	N
A/M	0.2361	likely_benign	0.2147	benign	-0.582	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
A/N	0.2023	likely_benign	0.1821	benign	-0.338	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
A/P	0.3346	likely_benign	0.246	benign	-0.368	Destabilizing	0.999	D	0.603	neutral	N	0.495354013	None	None	N
A/Q	0.3099	likely_benign	0.3129	benign	-0.6	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	N
A/R	0.4122	ambiguous	0.4062	ambiguous	-0.129	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
A/S	0.0881	likely_benign	0.0823	benign	-0.528	Destabilizing	0.957	D	0.343	neutral	N	0.449176219	None	None	N
A/T	0.0848	likely_benign	0.0788	benign	-0.604	Destabilizing	0.992	D	0.489	neutral	N	0.444135759	None	None	N
A/V	0.1364	likely_benign	0.1228	benign	-0.368	Destabilizing	0.998	D	0.511	neutral	N	0.482174072	None	None	N
A/W	0.7493	likely_pathogenic	0.7209	pathogenic	-1.018	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
A/Y	0.4813	ambiguous	0.441	ambiguous	-0.712	Destabilizing	1.0	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.