TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16396	49411;49412;49413	chr2:178614211;178614210;178614209	chr2:179478938;179478937;179478936
N2AB	14755	44488;44489;44490	chr2:178614211;178614210;178614209	chr2:179478938;179478937;179478936
N2A	13828	41707;41708;41709	chr2:178614211;178614210;178614209	chr2:179478938;179478937;179478936
N2B	7331	22216;22217;22218	chr2:178614211;178614210;178614209	chr2:179478938;179478937;179478936
Novex-1	7456	22591;22592;22593	chr2:178614211;178614210;178614209	chr2:179478938;179478937;179478936
Novex-2	7523	22792;22793;22794	chr2:178614211;178614210;178614209	chr2:179478938;179478937;179478936
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: Fn3-6
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9084
• 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/K	None	None	0.334	N	0.543	0.242	0.285698343383	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1429	likely_benign	0.1403	benign	-0.072	Destabilizing	0.334	N	0.547	neutral	N	0.484602361	None	None	N
E/C	0.799	likely_pathogenic	0.7875	pathogenic	-0.237	Destabilizing	0.982	D	0.693	prob.neutral	None	None	None	None	N
E/D	0.0799	likely_benign	0.0839	benign	-0.358	Destabilizing	0.001	N	0.389	neutral	N	0.474281563	None	None	N
E/F	0.722	likely_pathogenic	0.7129	pathogenic	-0.057	Destabilizing	0.982	D	0.624	neutral	None	None	None	None	N
E/G	0.1597	likely_benign	0.1559	benign	-0.195	Destabilizing	0.334	N	0.441	neutral	N	0.462473847	None	None	N
E/H	0.4271	ambiguous	0.4357	ambiguous	0.564	Stabilizing	0.947	D	0.59	neutral	None	None	None	None	N
E/I	0.3541	ambiguous	0.3549	ambiguous	0.198	Stabilizing	0.826	D	0.63	neutral	None	None	None	None	N
E/K	0.1643	likely_benign	0.1675	benign	0.411	Stabilizing	0.334	N	0.543	neutral	N	0.43684976	None	None	N
E/L	0.351	ambiguous	0.3526	ambiguous	0.198	Stabilizing	0.7	D	0.616	neutral	None	None	None	None	N
E/M	0.4266	ambiguous	0.4218	ambiguous	-0.025	Destabilizing	0.982	D	0.595	neutral	None	None	None	None	N
E/N	0.1743	likely_benign	0.1731	benign	0.087	Stabilizing	0.539	D	0.527	neutral	None	None	None	None	N
E/P	0.3326	likely_benign	0.3399	benign	0.126	Stabilizing	0.826	D	0.557	neutral	None	None	None	None	N
E/Q	0.1786	likely_benign	0.1876	benign	0.107	Stabilizing	0.638	D	0.522	neutral	N	0.47946017	None	None	N
E/R	0.3078	likely_benign	0.3172	benign	0.671	Stabilizing	0.7	D	0.572	neutral	None	None	None	None	N
E/S	0.1528	likely_benign	0.1535	benign	-0.034	Destabilizing	0.25	N	0.534	neutral	None	None	None	None	N
E/T	0.175	likely_benign	0.1755	benign	0.078	Stabilizing	0.7	D	0.531	neutral	None	None	None	None	N
E/V	0.2138	likely_benign	0.2129	benign	0.126	Stabilizing	0.781	D	0.567	neutral	N	0.48658697	None	None	N
E/W	0.8848	likely_pathogenic	0.8808	pathogenic	0.013	Stabilizing	0.982	D	0.699	prob.neutral	None	None	None	None	N
E/Y	0.6028	likely_pathogenic	0.5903	pathogenic	0.172	Stabilizing	0.982	D	0.583	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.