TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29145	87658;87659;87660	chr2:178557921;178557920;178557919	chr2:179422648;179422647;179422646
N2AB	27504	82735;82736;82737	chr2:178557921;178557920;178557919	chr2:179422648;179422647;179422646
N2A	26577	79954;79955;79956	chr2:178557921;178557920;178557919	chr2:179422648;179422647;179422646
N2B	20080	60463;60464;60465	chr2:178557921;178557920;178557919	chr2:179422648;179422647;179422646
Novex-1	20205	60838;60839;60840	chr2:178557921;178557920;178557919	chr2:179422648;179422647;179422646
Novex-2	20272	61039;61040;61041	chr2:178557921;178557920;178557919	chr2:179422648;179422647;179422646
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-100
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.0927
• 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
V/A	None	None	0.977	N	0.681	0.343	0.56977568999	gnomAD-4.0.0	3.42209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49713E-06	0	0
V/I	None	None	0.117	N	0.325	0.05	0.33110744837	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.4448	ambiguous	0.5238	ambiguous	-1.304	Destabilizing	0.977	D	0.681	prob.neutral	N	0.494075531	None	None	N
V/C	0.9147	likely_pathogenic	0.9154	pathogenic	-1.022	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
V/D	0.9855	likely_pathogenic	0.9907	pathogenic	-0.78	Destabilizing	0.999	D	0.837	deleterious	N	0.517206215	None	None	N
V/E	0.9679	likely_pathogenic	0.976	pathogenic	-0.673	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
V/F	0.6468	likely_pathogenic	0.6897	pathogenic	-0.679	Destabilizing	0.993	D	0.766	deleterious	N	0.482692772	None	None	N
V/G	0.8275	likely_pathogenic	0.8642	pathogenic	-1.73	Destabilizing	0.997	D	0.836	deleterious	N	0.517966684	None	None	N
V/H	0.9898	likely_pathogenic	0.9917	pathogenic	-1.345	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/I	0.091	likely_benign	0.0909	benign	-0.2	Destabilizing	0.117	N	0.325	neutral	N	0.472346654	None	None	N
V/K	0.9821	likely_pathogenic	0.9846	pathogenic	-1.074	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
V/L	0.3703	ambiguous	0.3767	ambiguous	-0.2	Destabilizing	0.898	D	0.675	prob.neutral	N	0.458118202	None	None	N
V/M	0.3955	ambiguous	0.4137	ambiguous	-0.32	Destabilizing	0.995	D	0.781	deleterious	None	None	None	None	N
V/N	0.9586	likely_pathogenic	0.9679	pathogenic	-1.071	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
V/P	0.7513	likely_pathogenic	0.8528	pathogenic	-0.533	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/Q	0.97	likely_pathogenic	0.9757	pathogenic	-1.011	Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
V/R	0.9717	likely_pathogenic	0.9742	pathogenic	-0.884	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
V/S	0.8376	likely_pathogenic	0.8719	pathogenic	-1.741	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
V/T	0.6119	likely_pathogenic	0.6526	pathogenic	-1.492	Destabilizing	0.983	D	0.699	prob.neutral	None	None	None	None	N
V/W	0.9912	likely_pathogenic	0.993	pathogenic	-0.988	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Y	0.9632	likely_pathogenic	0.9695	pathogenic	-0.616	Destabilizing	0.998	D	0.776	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.