TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26553	79882;79883;79884	chr2:178566475;178566474;178566473	chr2:179431202;179431201;179431200
N2AB	24912	74959;74960;74961	chr2:178566475;178566474;178566473	chr2:179431202;179431201;179431200
N2A	23985	72178;72179;72180	chr2:178566475;178566474;178566473	chr2:179431202;179431201;179431200
N2B	17488	52687;52688;52689	chr2:178566475;178566474;178566473	chr2:179431202;179431201;179431200
Novex-1	17613	53062;53063;53064	chr2:178566475;178566474;178566473	chr2:179431202;179431201;179431200
Novex-2	17680	53263;53264;53265	chr2:178566475;178566474;178566473	chr2:179431202;179431201;179431200
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-81
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.1291
• 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
L/P	rs1705907703	None	1.0	D	0.782	0.867	0.927379958638	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1705907703	None	1.0	D	0.782	0.867	0.927379958638	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-05	0	0
L/V	None	None	0.999	D	0.824	0.628	0.817017901033	gnomAD-4.0.0	6.84334E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99505E-07	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
L/A	0.8607	likely_pathogenic	0.8675	pathogenic	-2.436	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
L/C	0.8489	likely_pathogenic	0.8653	pathogenic	-2.068	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
L/D	0.9972	likely_pathogenic	0.9973	pathogenic	-1.945	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/E	0.9863	likely_pathogenic	0.9861	pathogenic	-1.779	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/F	0.7286	likely_pathogenic	0.7432	pathogenic	-1.677	Destabilizing	1.0	D	0.849	deleterious	D	0.647331728	None	None	N
L/G	0.9679	likely_pathogenic	0.9719	pathogenic	-2.93	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/H	0.9763	likely_pathogenic	0.9768	pathogenic	-2.174	Highly Destabilizing	1.0	D	0.739	prob.delet.	D	0.673677057	None	None	N
L/I	0.2474	likely_benign	0.2278	benign	-1.047	Destabilizing	0.999	D	0.816	deleterious	D	0.639822096	None	None	N
L/K	0.9723	likely_pathogenic	0.9759	pathogenic	-1.677	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/M	0.3233	likely_benign	0.3396	benign	-1.09	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/N	0.9815	likely_pathogenic	0.9821	pathogenic	-1.857	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
L/P	0.9755	likely_pathogenic	0.976	pathogenic	-1.486	Destabilizing	1.0	D	0.782	deleterious	D	0.673677057	None	None	N
L/Q	0.9473	likely_pathogenic	0.9499	pathogenic	-1.818	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/R	0.9532	likely_pathogenic	0.9577	pathogenic	-1.297	Destabilizing	1.0	D	0.786	deleterious	D	0.673677057	None	None	N
L/S	0.9799	likely_pathogenic	0.9807	pathogenic	-2.703	Highly Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/T	0.8969	likely_pathogenic	0.8963	pathogenic	-2.381	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/V	0.2455	likely_benign	0.2355	benign	-1.486	Destabilizing	0.999	D	0.824	deleterious	D	0.602089981	None	None	N
L/W	0.9594	likely_pathogenic	0.9628	pathogenic	-1.84	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
L/Y	0.9501	likely_pathogenic	0.9573	pathogenic	-1.584	Destabilizing	1.0	D	0.783	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.