TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29320	88183;88184;88185	chr2:178557304;178557303;178557302	chr2:179422031;179422030;179422029
N2AB	27679	83260;83261;83262	chr2:178557304;178557303;178557302	chr2:179422031;179422030;179422029
N2A	26752	80479;80480;80481	chr2:178557304;178557303;178557302	chr2:179422031;179422030;179422029
N2B	20255	60988;60989;60990	chr2:178557304;178557303;178557302	chr2:179422031;179422030;179422029
Novex-1	20380	61363;61364;61365	chr2:178557304;178557303;178557302	chr2:179422031;179422030;179422029
Novex-2	20447	61564;61565;61566	chr2:178557304;178557303;178557302	chr2:179422031;179422030;179422029
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: Fn3-101
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.2751
• 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
V/I	rs765724248	-0.915	None	N	0.275	0.129	0.144782658237	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	4.97611E-04	0	None	0	None	0	0	0
V/I	rs765724248	-0.915	None	N	0.275	0.129	0.144782658237	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	2.88351E-04	0	None	0	0	0	0	0
V/I	rs765724248	-0.915	None	N	0.275	0.129	0.144782658237	gnomAD-4.0.0	1.11535E-05	None	None	None	None	I	None	0	0	None	4.05405E-04	0	None	0	0	2.54262E-06	0	4.80338E-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
V/A	0.1493	likely_benign	0.1386	benign	-1.347	Destabilizing	0.104	N	0.623	neutral	N	0.47661075	None	None	I
V/C	0.5611	ambiguous	0.5451	ambiguous	-1.013	Destabilizing	0.968	D	0.773	deleterious	None	None	None	None	I
V/D	0.5778	likely_pathogenic	0.4934	ambiguous	-0.808	Destabilizing	0.667	D	0.839	deleterious	N	0.521228318	None	None	I
V/E	0.4242	ambiguous	0.3581	ambiguous	-0.843	Destabilizing	0.726	D	0.833	deleterious	None	None	None	None	I
V/F	0.1525	likely_benign	0.1309	benign	-1.164	Destabilizing	0.497	N	0.789	deleterious	N	0.505336146	None	None	I
V/G	0.2989	likely_benign	0.2693	benign	-1.619	Destabilizing	0.667	D	0.827	deleterious	N	0.521921752	None	None	I
V/H	0.591	likely_pathogenic	0.5262	ambiguous	-0.999	Destabilizing	0.968	D	0.836	deleterious	None	None	None	None	I
V/I	0.0556	likely_benign	0.057	benign	-0.722	Destabilizing	None	N	0.275	neutral	N	0.397149888	None	None	I
V/K	0.3606	ambiguous	0.317	benign	-0.927	Destabilizing	0.726	D	0.831	deleterious	None	None	None	None	I
V/L	0.1274	likely_benign	0.1235	benign	-0.722	Destabilizing	0.009	N	0.439	neutral	N	0.423122981	None	None	I
V/M	0.1112	likely_benign	0.1109	benign	-0.598	Destabilizing	0.567	D	0.736	prob.delet.	None	None	None	None	I
V/N	0.3327	likely_benign	0.2885	benign	-0.683	Destabilizing	0.89	D	0.843	deleterious	None	None	None	None	I
V/P	0.3668	ambiguous	0.3829	ambiguous	-0.894	Destabilizing	0.89	D	0.837	deleterious	None	None	None	None	I
V/Q	0.3728	ambiguous	0.3388	benign	-0.905	Destabilizing	0.89	D	0.834	deleterious	None	None	None	None	I
V/R	0.31	likely_benign	0.2573	benign	-0.363	Destabilizing	0.726	D	0.843	deleterious	None	None	None	None	I
V/S	0.2273	likely_benign	0.2002	benign	-1.251	Destabilizing	0.726	D	0.794	deleterious	None	None	None	None	I
V/T	0.1231	likely_benign	0.107	benign	-1.17	Destabilizing	0.272	N	0.676	prob.neutral	None	None	None	None	I
V/W	0.7285	likely_pathogenic	0.6755	pathogenic	-1.226	Destabilizing	0.968	D	0.801	deleterious	None	None	None	None	I
V/Y	0.4879	ambiguous	0.4607	ambiguous	-0.956	Destabilizing	0.726	D	0.781	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.