TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16370	49333;49334;49335	chr2:178614289;178614288;178614287	chr2:179479016;179479015;179479014
N2AB	14729	44410;44411;44412	chr2:178614289;178614288;178614287	chr2:179479016;179479015;179479014
N2A	13802	41629;41630;41631	chr2:178614289;178614288;178614287	chr2:179479016;179479015;179479014
N2B	7305	22138;22139;22140	chr2:178614289;178614288;178614287	chr2:179479016;179479015;179479014
Novex-1	7430	22513;22514;22515	chr2:178614289;178614288;178614287	chr2:179479016;179479015;179479014
Novex-2	7497	22714;22715;22716	chr2:178614289;178614288;178614287	chr2:179479016;179479015;179479014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-6
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0665
• 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	None	None	1.0	D	0.922	0.713	0.884904973826	gnomAD-4.0.0	1.59322E-06	None	None	None	None	N	None	0	0	None	0	2.78505E-05	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
L/A	0.9549	likely_pathogenic	0.9408	pathogenic	-2.374	Highly Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
L/C	0.8802	likely_pathogenic	0.8583	pathogenic	-1.216	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9998	pathogenic	-2.927	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.9987	pathogenic	-2.608	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/F	0.6015	likely_pathogenic	0.5558	ambiguous	-1.405	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
L/G	0.9947	likely_pathogenic	0.9924	pathogenic	-2.943	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/H	0.9964	likely_pathogenic	0.9949	pathogenic	-2.85	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/I	0.202	likely_benign	0.194	benign	-0.639	Destabilizing	0.999	D	0.536	neutral	D	0.578341333	None	None	N
L/K	0.9981	likely_pathogenic	0.9974	pathogenic	-1.614	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/M	0.3318	likely_benign	0.3178	benign	-0.846	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
L/N	0.999	likely_pathogenic	0.9987	pathogenic	-2.399	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/P	0.9976	likely_pathogenic	0.9963	pathogenic	-1.213	Destabilizing	1.0	D	0.922	deleterious	D	0.814198315	None	None	N
L/Q	0.9941	likely_pathogenic	0.9922	pathogenic	-1.947	Destabilizing	1.0	D	0.915	deleterious	D	0.814198315	None	None	N
L/R	0.996	likely_pathogenic	0.9945	pathogenic	-1.995	Destabilizing	1.0	D	0.893	deleterious	D	0.814198315	None	None	N
L/S	0.9971	likely_pathogenic	0.996	pathogenic	-2.767	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/T	0.9881	likely_pathogenic	0.9842	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/V	0.2505	likely_benign	0.2314	benign	-1.213	Destabilizing	0.999	D	0.558	neutral	N	0.486038895	None	None	N
L/W	0.9849	likely_pathogenic	0.9786	pathogenic	-1.671	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/Y	0.9847	likely_pathogenic	0.9789	pathogenic	-1.563	Destabilizing	1.0	D	0.811	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.