TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29233	87922;87923;87924	chr2:178557657;178557656;178557655	chr2:179422384;179422383;179422382
N2AB	27592	82999;83000;83001	chr2:178557657;178557656;178557655	chr2:179422384;179422383;179422382
N2A	26665	80218;80219;80220	chr2:178557657;178557656;178557655	chr2:179422384;179422383;179422382
N2B	20168	60727;60728;60729	chr2:178557657;178557656;178557655	chr2:179422384;179422383;179422382
Novex-1	20293	61102;61103;61104	chr2:178557657;178557656;178557655	chr2:179422384;179422383;179422382
Novex-2	20360	61303;61304;61305	chr2:178557657;178557656;178557655	chr2:179422384;179422383;179422382
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: Fn3-100
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.8882
• Predicted PPI site: I

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/V	rs1702051933	None	0.997	N	0.561	0.163	0.546952355657	gnomAD-4.0.0	1.59143E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02425E-05

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	0.5834	likely_pathogenic	0.583	pathogenic	-0.41	Destabilizing	0.998	D	0.728	deleterious	None	None	None	None	I
L/C	0.7039	likely_pathogenic	0.7321	pathogenic	-0.688	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	I
L/D	0.8697	likely_pathogenic	0.8978	pathogenic	-0.308	Destabilizing	1.0	D	0.688	prob.delet.	None	None	None	None	I
L/E	0.7045	likely_pathogenic	0.7202	pathogenic	-0.4	Destabilizing	0.999	D	0.697	prob.delet.	None	None	None	None	I
L/F	0.1937	likely_benign	0.1961	benign	-0.542	Destabilizing	0.999	D	0.729	deleterious	None	None	None	None	I
L/G	0.7778	likely_pathogenic	0.7904	pathogenic	-0.527	Destabilizing	0.999	D	0.685	prob.delet.	None	None	None	None	I
L/H	0.311	likely_benign	0.3218	benign	0.12	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
L/I	0.2656	likely_benign	0.2772	benign	-0.224	Destabilizing	0.997	D	0.524	neutral	N	0.447693352	None	None	I
L/K	0.4334	ambiguous	0.4437	ambiguous	-0.324	Destabilizing	0.999	D	0.695	prob.delet.	None	None	None	None	I
L/M	0.1755	likely_benign	0.1902	benign	-0.525	Destabilizing	0.999	D	0.725	deleterious	None	None	None	None	I
L/N	0.5499	ambiguous	0.6061	pathogenic	-0.164	Destabilizing	1.0	D	0.695	prob.delet.	None	None	None	None	I
L/P	0.4487	ambiguous	0.477	ambiguous	-0.257	Destabilizing	1.0	D	0.697	prob.delet.	N	0.453965963	None	None	I
L/Q	0.3122	likely_benign	0.3231	benign	-0.359	Destabilizing	1.0	D	0.684	prob.delet.	N	0.448213427	None	None	I
L/R	0.3493	ambiguous	0.3561	ambiguous	0.16	Stabilizing	0.999	D	0.694	prob.delet.	N	0.453792605	None	None	I
L/S	0.5744	likely_pathogenic	0.6007	pathogenic	-0.527	Destabilizing	0.999	D	0.704	prob.delet.	None	None	None	None	I
L/T	0.5855	likely_pathogenic	0.6226	pathogenic	-0.518	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
L/V	0.2719	likely_benign	0.2896	benign	-0.257	Destabilizing	0.997	D	0.561	neutral	N	0.490540052	None	None	I
L/W	0.2967	likely_benign	0.3002	benign	-0.575	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	I
L/Y	0.3088	likely_benign	0.3041	benign	-0.327	Destabilizing	0.999	D	0.724	deleterious	None	None	None	None	I

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.