TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27092	81499;81500;81501	chr2:178564858;178564857;178564856	chr2:179429585;179429584;179429583
N2AB	25451	76576;76577;76578	chr2:178564858;178564857;178564856	chr2:179429585;179429584;179429583
N2A	24524	73795;73796;73797	chr2:178564858;178564857;178564856	chr2:179429585;179429584;179429583
N2B	18027	54304;54305;54306	chr2:178564858;178564857;178564856	chr2:179429585;179429584;179429583
Novex-1	18152	54679;54680;54681	chr2:178564858;178564857;178564856	chr2:179429585;179429584;179429583
Novex-2	18219	54880;54881;54882	chr2:178564858;178564857;178564856	chr2:179429585;179429584;179429583
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-85
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3422
• 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
Q/L	rs950280958	0.637	0.062	N	0.502	0.167	0.405979908929	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
Q/L	rs950280958	0.637	0.062	N	0.502	0.167	0.405979908929	gnomAD-4.0.0	1.59306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.436E-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
Q/A	0.195	likely_benign	0.2014	benign	-1.057	Destabilizing	0.035	N	0.471	neutral	None	None	None	None	N
Q/C	0.3782	ambiguous	0.4336	ambiguous	-0.403	Destabilizing	0.935	D	0.597	neutral	None	None	None	None	N
Q/D	0.448	ambiguous	0.4833	ambiguous	-1.872	Destabilizing	0.035	N	0.423	neutral	None	None	None	None	N
Q/E	0.0827	likely_benign	0.076	benign	-1.582	Destabilizing	None	N	0.192	neutral	N	0.386839681	None	None	N
Q/F	0.5746	likely_pathogenic	0.655	pathogenic	-0.433	Destabilizing	0.555	D	0.585	neutral	None	None	None	None	N
Q/G	0.2841	likely_benign	0.2955	benign	-1.501	Destabilizing	0.149	N	0.515	neutral	None	None	None	None	N
Q/H	0.1566	likely_benign	0.2034	benign	-1.046	Destabilizing	0.484	N	0.519	neutral	N	0.474768097	None	None	N
Q/I	0.3067	likely_benign	0.3404	ambiguous	0.171	Stabilizing	0.38	N	0.599	neutral	None	None	None	None	N
Q/K	0.1246	likely_benign	0.1207	benign	-0.575	Destabilizing	0.027	N	0.455	neutral	N	0.455854262	None	None	N
Q/L	0.1313	likely_benign	0.1479	benign	0.171	Stabilizing	0.062	N	0.502	neutral	N	0.472978586	None	None	N
Q/M	0.2813	likely_benign	0.3008	benign	0.29	Stabilizing	0.791	D	0.523	neutral	None	None	None	None	N
Q/N	0.2636	likely_benign	0.3157	benign	-1.378	Destabilizing	0.149	N	0.397	neutral	None	None	None	None	N
Q/P	0.8513	likely_pathogenic	0.8768	pathogenic	-0.215	Destabilizing	0.211	N	0.522	neutral	N	0.483182844	None	None	N
Q/R	0.124	likely_benign	0.1239	benign	-0.781	Destabilizing	0.062	N	0.407	neutral	N	0.457046341	None	None	N
Q/S	0.1937	likely_benign	0.205	benign	-1.631	Destabilizing	0.035	N	0.422	neutral	None	None	None	None	N
Q/T	0.1522	likely_benign	0.1508	benign	-1.168	Destabilizing	0.002	N	0.333	neutral	None	None	None	None	N
Q/V	0.1867	likely_benign	0.2058	benign	-0.215	Destabilizing	0.081	N	0.511	neutral	None	None	None	None	N
Q/W	0.5413	ambiguous	0.5839	pathogenic	-0.58	Destabilizing	0.935	D	0.609	neutral	None	None	None	None	N
Q/Y	0.3536	ambiguous	0.4279	ambiguous	-0.17	Destabilizing	0.791	D	0.573	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.