TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29361	88306;88307;88308	chr2:178557073;178557072;178557071	chr2:179421800;179421799;179421798
N2AB	27720	83383;83384;83385	chr2:178557073;178557072;178557071	chr2:179421800;179421799;179421798
N2A	26793	80602;80603;80604	chr2:178557073;178557072;178557071	chr2:179421800;179421799;179421798
N2B	20296	61111;61112;61113	chr2:178557073;178557072;178557071	chr2:179421800;179421799;179421798
Novex-1	20421	61486;61487;61488	chr2:178557073;178557072;178557071	chr2:179421800;179421799;179421798
Novex-2	20488	61687;61688;61689	chr2:178557073;178557072;178557071	chr2:179421800;179421799;179421798
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-102
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.7294
• 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
F/L	rs746746013	None	0.625	N	0.374	0.184	0.0297737177859	gnomAD-4.0.0	6.84284E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99475E-07	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
F/A	0.7251	likely_pathogenic	0.6236	pathogenic	-1.011	Destabilizing	0.842	D	0.401	neutral	None	None	None	None	I
F/C	0.5767	likely_pathogenic	0.4422	ambiguous	-0.201	Destabilizing	0.997	D	0.369	neutral	N	0.455639208	None	None	I
F/D	0.8569	likely_pathogenic	0.8073	pathogenic	0.713	Stabilizing	0.974	D	0.385	neutral	None	None	None	None	I
F/E	0.9134	likely_pathogenic	0.8773	pathogenic	0.68	Stabilizing	0.949	D	0.386	neutral	None	None	None	None	I
F/G	0.8348	likely_pathogenic	0.7564	pathogenic	-1.21	Destabilizing	0.915	D	0.434	neutral	None	None	None	None	I
F/H	0.6404	likely_pathogenic	0.5503	ambiguous	0.154	Stabilizing	0.949	D	0.355	neutral	None	None	None	None	I
F/I	0.5948	likely_pathogenic	0.4804	ambiguous	-0.508	Destabilizing	0.891	D	0.384	neutral	N	0.466865398	None	None	I
F/K	0.9172	likely_pathogenic	0.8858	pathogenic	-0.003	Destabilizing	0.949	D	0.383	neutral	None	None	None	None	I
F/L	0.945	likely_pathogenic	0.9072	pathogenic	-0.508	Destabilizing	0.625	D	0.374	neutral	N	0.4718285	None	None	I
F/M	0.7255	likely_pathogenic	0.6392	pathogenic	-0.269	Destabilizing	0.991	D	0.345	neutral	None	None	None	None	I
F/N	0.6523	likely_pathogenic	0.559	ambiguous	0.127	Stabilizing	0.991	D	0.401	neutral	None	None	None	None	I
F/P	0.9947	likely_pathogenic	0.9902	pathogenic	-0.656	Destabilizing	0.016	N	0.293	neutral	None	None	None	None	I
F/Q	0.8623	likely_pathogenic	0.8043	pathogenic	0.006	Stabilizing	0.991	D	0.399	neutral	None	None	None	None	I
F/R	0.8379	likely_pathogenic	0.7801	pathogenic	0.524	Stabilizing	0.974	D	0.402	neutral	None	None	None	None	I
F/S	0.5396	ambiguous	0.4222	ambiguous	-0.585	Destabilizing	0.801	D	0.417	neutral	N	0.390327412	None	None	I
F/T	0.6724	likely_pathogenic	0.5776	pathogenic	-0.525	Destabilizing	0.915	D	0.401	neutral	None	None	None	None	I
F/V	0.5167	ambiguous	0.4085	ambiguous	-0.656	Destabilizing	0.801	D	0.423	neutral	N	0.474330088	None	None	I
F/W	0.536	ambiguous	0.4547	ambiguous	-0.382	Destabilizing	0.974	D	0.361	neutral	None	None	None	None	I
F/Y	0.1466	likely_benign	0.1142	benign	-0.31	Destabilizing	0.007	N	0.091	neutral	N	0.350329016	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.