TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25667	77224;77225;77226	chr2:178569133;178569132;178569131	chr2:179433860;179433859;179433858
N2AB	24026	72301;72302;72303	chr2:178569133;178569132;178569131	chr2:179433860;179433859;179433858
N2A	23099	69520;69521;69522	chr2:178569133;178569132;178569131	chr2:179433860;179433859;179433858
N2B	16602	50029;50030;50031	chr2:178569133;178569132;178569131	chr2:179433860;179433859;179433858
Novex-1	16727	50404;50405;50406	chr2:178569133;178569132;178569131	chr2:179433860;179433859;179433858
Novex-2	16794	50605;50606;50607	chr2:178569133;178569132;178569131	chr2:179433860;179433859;179433858
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-74
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.5052
• 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
E/G	rs777038781	-0.949	1.0	N	0.607	0.555	0.656895726345	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/G	rs777038781	-0.949	1.0	N	0.607	0.555	0.656895726345	gnomAD-4.0.0	3.18409E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71994E-06	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
E/A	0.3852	ambiguous	0.3751	ambiguous	-0.382	Destabilizing	0.995	D	0.649	neutral	N	0.506435011	None	None	N
E/C	0.98	likely_pathogenic	0.979	pathogenic	-0.052	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/D	0.6296	likely_pathogenic	0.657	pathogenic	-0.367	Destabilizing	0.965	D	0.6	neutral	N	0.507870464	None	None	N
E/F	0.9875	likely_pathogenic	0.9862	pathogenic	-0.294	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
E/G	0.6353	likely_pathogenic	0.631	pathogenic	-0.594	Destabilizing	1.0	D	0.607	neutral	N	0.498084321	None	None	N
E/H	0.9547	likely_pathogenic	0.953	pathogenic	-0.16	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/I	0.8125	likely_pathogenic	0.7819	pathogenic	0.144	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/K	0.682	likely_pathogenic	0.6594	pathogenic	0.158	Stabilizing	0.997	D	0.707	prob.neutral	N	0.494348112	None	None	N
E/L	0.8947	likely_pathogenic	0.8813	pathogenic	0.144	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	N
E/M	0.8753	likely_pathogenic	0.8615	pathogenic	0.265	Stabilizing	0.998	D	0.595	neutral	None	None	None	None	N
E/N	0.8137	likely_pathogenic	0.8223	pathogenic	-0.047	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
E/P	0.7059	likely_pathogenic	0.7428	pathogenic	-0.01	Destabilizing	0.992	D	0.613	neutral	None	None	None	None	N
E/Q	0.452	ambiguous	0.4394	ambiguous	-0.02	Destabilizing	0.999	D	0.687	prob.neutral	N	0.472218159	None	None	N
E/R	0.8306	likely_pathogenic	0.8138	pathogenic	0.37	Stabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
E/S	0.6674	likely_pathogenic	0.67	pathogenic	-0.255	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	N
E/T	0.7237	likely_pathogenic	0.6864	pathogenic	-0.092	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/V	0.62	likely_pathogenic	0.5656	pathogenic	-0.01	Destabilizing	0.998	D	0.614	neutral	N	0.499147505	None	None	N
E/W	0.9968	likely_pathogenic	0.9965	pathogenic	-0.167	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/Y	0.9763	likely_pathogenic	0.9745	pathogenic	-0.062	Destabilizing	1.0	D	0.605	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.