TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31746	95461;95462;95463	chr2:178546000;178545999;178545998	chr2:179410727;179410726;179410725
N2AB	30105	90538;90539;90540	chr2:178546000;178545999;178545998	chr2:179410727;179410726;179410725
N2A	29178	87757;87758;87759	chr2:178546000;178545999;178545998	chr2:179410727;179410726;179410725
N2B	22681	68266;68267;68268	chr2:178546000;178545999;178545998	chr2:179410727;179410726;179410725
Novex-1	22806	68641;68642;68643	chr2:178546000;178545999;178545998	chr2:179410727;179410726;179410725
Novex-2	22873	68842;68843;68844	chr2:178546000;178545999;178545998	chr2:179410727;179410726;179410725
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: Fn3-119
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1108
• 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	D	0.799	0.584	0.500050830518	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.8858	likely_pathogenic	0.8847	pathogenic	-1.347	Destabilizing	0.999	D	0.747	deleterious	D	0.545560231	None	None	N
E/C	0.9883	likely_pathogenic	0.9881	pathogenic	-0.547	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/D	0.7739	likely_pathogenic	0.7365	pathogenic	-1.807	Destabilizing	0.999	D	0.677	prob.neutral	N	0.504832271	None	None	N
E/F	0.9949	likely_pathogenic	0.9948	pathogenic	-1.054	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/G	0.9306	likely_pathogenic	0.9155	pathogenic	-1.726	Destabilizing	1.0	D	0.799	deleterious	D	0.535813768	None	None	N
E/H	0.9794	likely_pathogenic	0.9807	pathogenic	-0.907	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/I	0.9888	likely_pathogenic	0.9877	pathogenic	-0.258	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
E/K	0.9685	likely_pathogenic	0.9642	pathogenic	-1.343	Destabilizing	0.999	D	0.683	prob.neutral	D	0.523719767	None	None	N
E/L	0.9828	likely_pathogenic	0.9797	pathogenic	-0.258	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/M	0.9764	likely_pathogenic	0.9742	pathogenic	0.416	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
E/N	0.9764	likely_pathogenic	0.9744	pathogenic	-1.602	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9997	pathogenic	-0.608	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/Q	0.6407	likely_pathogenic	0.6259	pathogenic	-1.298	Destabilizing	1.0	D	0.775	deleterious	N	0.470545864	None	None	N
E/R	0.9767	likely_pathogenic	0.974	pathogenic	-1.229	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/S	0.8642	likely_pathogenic	0.8575	pathogenic	-2.164	Highly Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
E/T	0.9685	likely_pathogenic	0.9649	pathogenic	-1.798	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/V	0.9682	likely_pathogenic	0.9648	pathogenic	-0.608	Destabilizing	1.0	D	0.799	deleterious	D	0.53479981	None	None	N
E/W	0.9975	likely_pathogenic	0.9977	pathogenic	-1.19	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/Y	0.9903	likely_pathogenic	0.9907	pathogenic	-0.876	Destabilizing	1.0	D	0.846	deleterious	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.