TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29137	87634;87635;87636	chr2:178557945;178557944;178557943	chr2:179422672;179422671;179422670
N2AB	27496	82711;82712;82713	chr2:178557945;178557944;178557943	chr2:179422672;179422671;179422670
N2A	26569	79930;79931;79932	chr2:178557945;178557944;178557943	chr2:179422672;179422671;179422670
N2B	20072	60439;60440;60441	chr2:178557945;178557944;178557943	chr2:179422672;179422671;179422670
Novex-1	20197	60814;60815;60816	chr2:178557945;178557944;178557943	chr2:179422672;179422671;179422670
Novex-2	20264	61015;61016;61017	chr2:178557945;178557944;178557943	chr2:179422672;179422671;179422670
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-100
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.39
• 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
R/G	None	None	0.988	N	0.535	0.291	0.364730456448	gnomAD-4.0.0	1.59303E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85776E-06	0	0
R/K	rs1210340832	None	0.355	N	0.263	0.14	0.163833314356	gnomAD-4.0.0	1.36909E-06	None	None	None	None	I	None	2.98686E-05	0	None	0	0	None	0	0	0	1.15931E-05	0
R/M	None	None	1.0	N	0.57	0.262	0.253726318573	gnomAD-4.0.0	6.84543E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99423E-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
R/A	0.6865	likely_pathogenic	0.6675	pathogenic	-0.319	Destabilizing	0.982	D	0.567	neutral	None	None	None	None	I
R/C	0.215	likely_benign	0.2108	benign	-0.34	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
R/D	0.9578	likely_pathogenic	0.9629	pathogenic	-0.053	Destabilizing	0.997	D	0.741	deleterious	None	None	None	None	I
R/E	0.7122	likely_pathogenic	0.7252	pathogenic	0.009	Stabilizing	0.982	D	0.467	neutral	None	None	None	None	I
R/F	0.8341	likely_pathogenic	0.8439	pathogenic	-0.519	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
R/G	0.6793	likely_pathogenic	0.6792	pathogenic	-0.527	Destabilizing	0.988	D	0.535	neutral	N	0.482038803	None	None	I
R/H	0.2004	likely_benign	0.208	benign	-0.894	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	I
R/I	0.4236	ambiguous	0.4136	ambiguous	0.2	Stabilizing	0.999	D	0.845	deleterious	None	None	None	None	I
R/K	0.1204	likely_benign	0.1128	benign	-0.319	Destabilizing	0.355	N	0.263	neutral	N	0.412532268	None	None	I
R/L	0.5079	ambiguous	0.5189	ambiguous	0.2	Stabilizing	0.991	D	0.535	neutral	None	None	None	None	I
R/M	0.5357	ambiguous	0.5401	ambiguous	-0.056	Destabilizing	1.0	D	0.57	neutral	N	0.470935987	None	None	I
R/N	0.8759	likely_pathogenic	0.8848	pathogenic	0.099	Stabilizing	0.997	D	0.573	neutral	None	None	None	None	I
R/P	0.7487	likely_pathogenic	0.7701	pathogenic	0.047	Stabilizing	0.999	D	0.842	deleterious	None	None	None	None	I
R/Q	0.1663	likely_benign	0.1664	benign	-0.118	Destabilizing	0.995	D	0.609	neutral	None	None	None	None	I
R/S	0.8019	likely_pathogenic	0.7964	pathogenic	-0.447	Destabilizing	0.976	D	0.706	prob.delet.	N	0.458819213	None	None	I
R/T	0.5655	likely_pathogenic	0.5432	ambiguous	-0.247	Destabilizing	0.997	D	0.557	neutral	N	0.489243612	None	None	I
R/V	0.5381	ambiguous	0.5236	ambiguous	0.047	Stabilizing	0.997	D	0.808	deleterious	None	None	None	None	I
R/W	0.493	ambiguous	0.5129	ambiguous	-0.427	Destabilizing	1.0	D	0.851	deleterious	N	0.482545782	None	None	I
R/Y	0.6896	likely_pathogenic	0.7062	pathogenic	-0.05	Destabilizing	0.999	D	0.833	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.