TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23991	72196;72197;72198	chr2:178574161;178574160;178574159	chr2:179438888;179438887;179438886
N2AB	22350	67273;67274;67275	chr2:178574161;178574160;178574159	chr2:179438888;179438887;179438886
N2A	21423	64492;64493;64494	chr2:178574161;178574160;178574159	chr2:179438888;179438887;179438886
N2B	14926	45001;45002;45003	chr2:178574161;178574160;178574159	chr2:179438888;179438887;179438886
Novex-1	15051	45376;45377;45378	chr2:178574161;178574160;178574159	chr2:179438888;179438887;179438886
Novex-2	15118	45577;45578;45579	chr2:178574161;178574160;178574159	chr2:179438888;179438887;179438886
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: Fn3-62
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.331
• 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	None	None	1.0	N	0.646	0.602	0.516381326315	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8591E-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	0.28	likely_benign	0.3232	benign	-0.504	Destabilizing	0.999	D	0.658	neutral	N	0.477823565	None	None	N
E/C	0.9792	likely_pathogenic	0.9794	pathogenic	-0.074	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.6387	likely_pathogenic	0.6609	pathogenic	-0.644	Destabilizing	0.999	D	0.565	neutral	N	0.484005764	None	None	N
E/F	0.9799	likely_pathogenic	0.9833	pathogenic	-0.538	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/G	0.4366	ambiguous	0.4931	ambiguous	-0.746	Destabilizing	1.0	D	0.646	neutral	N	0.495615559	None	None	N
E/H	0.9141	likely_pathogenic	0.9307	pathogenic	-0.683	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
E/I	0.7783	likely_pathogenic	0.8015	pathogenic	0.114	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/K	0.3541	ambiguous	0.4272	ambiguous	-0.26	Destabilizing	0.999	D	0.678	prob.neutral	N	0.485954321	None	None	N
E/L	0.8551	likely_pathogenic	0.8827	pathogenic	0.114	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/M	0.7931	likely_pathogenic	0.8222	pathogenic	0.442	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/N	0.7849	likely_pathogenic	0.8136	pathogenic	-0.347	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/P	0.6821	likely_pathogenic	0.7251	pathogenic	-0.071	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/Q	0.2741	likely_benign	0.3099	benign	-0.309	Destabilizing	1.0	D	0.663	neutral	N	0.469255644	None	None	N
E/R	0.5746	likely_pathogenic	0.6394	pathogenic	-0.099	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/S	0.5359	ambiguous	0.586	pathogenic	-0.587	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
E/T	0.5941	likely_pathogenic	0.6401	pathogenic	-0.411	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/V	0.5414	ambiguous	0.576	pathogenic	-0.071	Destabilizing	1.0	D	0.648	neutral	N	0.498324584	None	None	N
E/W	0.9947	likely_pathogenic	0.9956	pathogenic	-0.479	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/Y	0.9685	likely_pathogenic	0.9732	pathogenic	-0.346	Destabilizing	1.0	D	0.669	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.