TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29199	87820;87821;87822	chr2:178557759;178557758;178557757	chr2:179422486;179422485;179422484
N2AB	27558	82897;82898;82899	chr2:178557759;178557758;178557757	chr2:179422486;179422485;179422484
N2A	26631	80116;80117;80118	chr2:178557759;178557758;178557757	chr2:179422486;179422485;179422484
N2B	20134	60625;60626;60627	chr2:178557759;178557758;178557757	chr2:179422486;179422485;179422484
Novex-1	20259	61000;61001;61002	chr2:178557759;178557758;178557757	chr2:179422486;179422485;179422484
Novex-2	20326	61201;61202;61203	chr2:178557759;178557758;178557757	chr2:179422486;179422485;179422484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-100
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0945
• 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/L	None	None	0.031	N	0.409	0.054	0.496693547531	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
V/A	0.5128	ambiguous	0.568	pathogenic	-2.116	Highly Destabilizing	0.296	N	0.658	neutral	N	0.50296035	None	None	N
V/C	0.8476	likely_pathogenic	0.8588	pathogenic	-1.663	Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	N
V/D	0.9778	likely_pathogenic	0.983	pathogenic	-2.571	Highly Destabilizing	0.879	D	0.891	deleterious	N	0.498736793	None	None	N
V/E	0.95	likely_pathogenic	0.9549	pathogenic	-2.352	Highly Destabilizing	0.967	D	0.872	deleterious	None	None	None	None	N
V/F	0.4323	ambiguous	0.4735	ambiguous	-1.297	Destabilizing	0.782	D	0.817	deleterious	N	0.498163681	None	None	N
V/G	0.7627	likely_pathogenic	0.7932	pathogenic	-2.659	Highly Destabilizing	0.879	D	0.881	deleterious	D	0.542947474	None	None	N
V/H	0.9763	likely_pathogenic	0.9795	pathogenic	-2.329	Highly Destabilizing	0.991	D	0.879	deleterious	None	None	None	None	N
V/I	0.0777	likely_benign	0.0794	benign	-0.602	Destabilizing	0.001	N	0.175	neutral	N	0.470941145	None	None	N
V/K	0.9695	likely_pathogenic	0.9721	pathogenic	-1.87	Destabilizing	0.906	D	0.875	deleterious	None	None	None	None	N
V/L	0.3332	likely_benign	0.3443	ambiguous	-0.602	Destabilizing	0.031	N	0.409	neutral	N	0.510302036	None	None	N
V/M	0.3331	likely_benign	0.3732	ambiguous	-0.599	Destabilizing	0.826	D	0.686	prob.neutral	None	None	None	None	N
V/N	0.9246	likely_pathogenic	0.9414	pathogenic	-2.147	Highly Destabilizing	0.967	D	0.892	deleterious	None	None	None	None	N
V/P	0.9455	likely_pathogenic	0.9584	pathogenic	-1.079	Destabilizing	0.967	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9462	likely_pathogenic	0.9538	pathogenic	-1.992	Destabilizing	0.967	D	0.885	deleterious	None	None	None	None	N
V/R	0.9567	likely_pathogenic	0.9609	pathogenic	-1.702	Destabilizing	0.906	D	0.897	deleterious	None	None	None	None	N
V/S	0.824	likely_pathogenic	0.8616	pathogenic	-2.782	Highly Destabilizing	0.906	D	0.845	deleterious	None	None	None	None	N
V/T	0.7291	likely_pathogenic	0.7587	pathogenic	-2.404	Highly Destabilizing	0.575	D	0.663	neutral	None	None	None	None	N
V/W	0.9726	likely_pathogenic	0.9744	pathogenic	-1.749	Destabilizing	0.991	D	0.847	deleterious	None	None	None	None	N
V/Y	0.8925	likely_pathogenic	0.9091	pathogenic	-1.374	Destabilizing	0.906	D	0.806	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.