TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5863	17812;17813;17814	chr2:178731078;178731077;178731076	chr2:179595805;179595804;179595803
N2AB	5546	16861;16862;16863	chr2:178731078;178731077;178731076	chr2:179595805;179595804;179595803
N2A	4619	14080;14081;14082	chr2:178731078;178731077;178731076	chr2:179595805;179595804;179595803
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-42
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1633
• 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/Q	rs2080395213	None	1.0	D	0.869	0.826	0.885250842136	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
L/V	None	None	0.999	D	0.535	0.407	0.632750256606	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
L/A	0.8517	likely_pathogenic	0.8974	pathogenic	-2.164	Highly Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
L/C	0.8689	likely_pathogenic	0.9088	pathogenic	-1.319	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/D	0.9922	likely_pathogenic	0.9958	pathogenic	-2.673	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/E	0.9452	likely_pathogenic	0.9662	pathogenic	-2.397	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/F	0.4916	ambiguous	0.6053	pathogenic	-1.325	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/G	0.9674	likely_pathogenic	0.9806	pathogenic	-2.71	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/H	0.9061	likely_pathogenic	0.9434	pathogenic	-2.244	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/I	0.0945	likely_benign	0.1029	benign	-0.56	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
L/K	0.8984	likely_pathogenic	0.9325	pathogenic	-1.599	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/M	0.2031	likely_benign	0.2352	benign	-0.545	Destabilizing	1.0	D	0.781	deleterious	N	0.514519277	None	None	N
L/N	0.9597	likely_pathogenic	0.9765	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/P	0.9463	likely_pathogenic	0.9698	pathogenic	-1.08	Destabilizing	1.0	D	0.883	deleterious	D	0.536106252	None	None	N
L/Q	0.8431	likely_pathogenic	0.8895	pathogenic	-1.887	Destabilizing	1.0	D	0.869	deleterious	D	0.536359741	None	None	N
L/R	0.8613	likely_pathogenic	0.9066	pathogenic	-1.588	Destabilizing	1.0	D	0.867	deleterious	D	0.524749947	None	None	N
L/S	0.963	likely_pathogenic	0.9799	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/T	0.8646	likely_pathogenic	0.9107	pathogenic	-2.307	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/V	0.1512	likely_benign	0.1651	benign	-1.08	Destabilizing	0.999	D	0.535	neutral	D	0.539951018	None	None	N
L/W	0.8219	likely_pathogenic	0.8749	pathogenic	-1.7	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/Y	0.8649	likely_pathogenic	0.9084	pathogenic	-1.351	Destabilizing	1.0	D	0.858	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.