TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16619	50080;50081;50082	chr2:178612866;178612865;178612864	chr2:179477593;179477592;179477591
N2AB	14978	45157;45158;45159	chr2:178612866;178612865;178612864	chr2:179477593;179477592;179477591
N2A	14051	42376;42377;42378	chr2:178612866;178612865;178612864	chr2:179477593;179477592;179477591
N2B	7554	22885;22886;22887	chr2:178612866;178612865;178612864	chr2:179477593;179477592;179477591
Novex-1	7679	23260;23261;23262	chr2:178612866;178612865;178612864	chr2:179477593;179477592;179477591
Novex-2	7746	23461;23462;23463	chr2:178612866;178612865;178612864	chr2:179477593;179477592;179477591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-8
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.2069
• 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/H	rs754592165	None	0.999	N	0.625	0.233	0.32714864917	gnomAD-4.0.0	4.78153E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.30009E-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	0.4173	ambiguous	0.4177	ambiguous	-0.761	Destabilizing	0.997	D	0.415	neutral	None	None	None	None	N
Q/C	0.8946	likely_pathogenic	0.8909	pathogenic	-0.119	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
Q/D	0.7963	likely_pathogenic	0.8126	pathogenic	-1.243	Destabilizing	0.997	D	0.495	neutral	None	None	None	None	N
Q/E	0.1602	likely_benign	0.1675	benign	-1.079	Destabilizing	0.992	D	0.421	neutral	N	0.474068795	None	None	N
Q/F	0.9141	likely_pathogenic	0.9095	pathogenic	-0.289	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
Q/G	0.5735	likely_pathogenic	0.6	pathogenic	-1.18	Destabilizing	0.997	D	0.537	neutral	None	None	None	None	N
Q/H	0.632	likely_pathogenic	0.611	pathogenic	-1.074	Destabilizing	0.999	D	0.625	neutral	N	0.480070177	None	None	N
Q/I	0.6659	likely_pathogenic	0.6475	pathogenic	0.345	Stabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
Q/K	0.2648	likely_benign	0.2892	benign	-0.613	Destabilizing	0.997	D	0.417	neutral	N	0.47213553	None	None	N
Q/L	0.3538	ambiguous	0.348	ambiguous	0.345	Stabilizing	0.997	D	0.537	neutral	N	0.479879205	None	None	N
Q/M	0.4675	ambiguous	0.4432	ambiguous	0.797	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	N
Q/N	0.5572	ambiguous	0.535	ambiguous	-1.261	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
Q/P	0.9052	likely_pathogenic	0.9222	pathogenic	0.007	Stabilizing	0.999	D	0.623	neutral	D	0.603733746	None	None	N
Q/R	0.3314	likely_benign	0.3761	ambiguous	-0.672	Destabilizing	0.997	D	0.499	neutral	N	0.462192985	None	None	N
Q/S	0.4753	ambiguous	0.4736	ambiguous	-1.356	Destabilizing	0.997	D	0.431	neutral	None	None	None	None	N
Q/T	0.3711	ambiguous	0.3606	ambiguous	-0.998	Destabilizing	0.999	D	0.532	neutral	None	None	None	None	N
Q/V	0.4623	ambiguous	0.4508	ambiguous	0.007	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
Q/W	0.9146	likely_pathogenic	0.9252	pathogenic	-0.281	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
Q/Y	0.8554	likely_pathogenic	0.8488	pathogenic	-0.003	Destabilizing	0.999	D	0.598	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.