TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30668	92227;92228;92229	chr2:178549720;178549719;178549718	chr2:179414447;179414446;179414445
N2AB	29027	87304;87305;87306	chr2:178549720;178549719;178549718	chr2:179414447;179414446;179414445
N2A	28100	84523;84524;84525	chr2:178549720;178549719;178549718	chr2:179414447;179414446;179414445
N2B	21603	65032;65033;65034	chr2:178549720;178549719;178549718	chr2:179414447;179414446;179414445
Novex-1	21728	65407;65408;65409	chr2:178549720;178549719;178549718	chr2:179414447;179414446;179414445
Novex-2	21795	65608;65609;65610	chr2:178549720;178549719;178549718	chr2:179414447;179414446;179414445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-111
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.3478
• 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
A/T	None	None	1.0	N	0.669	0.359	0.290962096972	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-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
A/C	0.7307	likely_pathogenic	0.733	pathogenic	-0.697	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
A/D	0.885	likely_pathogenic	0.8992	pathogenic	-0.737	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
A/E	0.841	likely_pathogenic	0.8534	pathogenic	-0.782	Destabilizing	1.0	D	0.75	deleterious	N	0.46041472	None	None	N
A/F	0.6562	likely_pathogenic	0.715	pathogenic	-0.767	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/G	0.3387	likely_benign	0.3718	ambiguous	-0.842	Destabilizing	1.0	D	0.568	neutral	N	0.498106317	None	None	N
A/H	0.8286	likely_pathogenic	0.8187	pathogenic	-0.832	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
A/I	0.5227	ambiguous	0.5463	ambiguous	-0.23	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
A/K	0.9231	likely_pathogenic	0.9248	pathogenic	-0.988	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
A/L	0.4136	ambiguous	0.429	ambiguous	-0.23	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
A/M	0.4027	ambiguous	0.4235	ambiguous	-0.296	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
A/N	0.5513	ambiguous	0.5463	ambiguous	-0.769	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/P	0.9526	likely_pathogenic	0.9556	pathogenic	-0.324	Destabilizing	1.0	D	0.737	prob.delet.	D	0.522540614	None	None	N
A/Q	0.715	likely_pathogenic	0.7027	pathogenic	-0.923	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
A/R	0.881	likely_pathogenic	0.8788	pathogenic	-0.586	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/S	0.1509	likely_benign	0.1535	benign	-1.079	Destabilizing	1.0	D	0.557	neutral	N	0.427571583	None	None	N
A/T	0.1663	likely_benign	0.1891	benign	-1.032	Destabilizing	1.0	D	0.669	neutral	N	0.349110799	None	None	N
A/V	0.2546	likely_benign	0.2826	benign	-0.324	Destabilizing	1.0	D	0.616	neutral	N	0.397518035	None	None	N
A/W	0.9565	likely_pathogenic	0.9596	pathogenic	-1.08	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
A/Y	0.8065	likely_pathogenic	0.8152	pathogenic	-0.67	Destabilizing	1.0	D	0.716	prob.delet.	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.