TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29142	87649;87650;87651	chr2:178557930;178557929;178557928	chr2:179422657;179422656;179422655
N2AB	27501	82726;82727;82728	chr2:178557930;178557929;178557928	chr2:179422657;179422656;179422655
N2A	26574	79945;79946;79947	chr2:178557930;178557929;178557928	chr2:179422657;179422656;179422655
N2B	20077	60454;60455;60456	chr2:178557930;178557929;178557928	chr2:179422657;179422656;179422655
Novex-1	20202	60829;60830;60831	chr2:178557930;178557929;178557928	chr2:179422657;179422656;179422655
Novex-2	20269	61030;61031;61032	chr2:178557930;178557929;178557928	chr2:179422657;179422656;179422655
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-100
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.33
• 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
T/A	rs1196119784	None	0.019	N	0.361	0.072	0.137902524267	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
T/A	rs1196119784	None	0.019	N	0.361	0.072	0.137902524267	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	1.92753E-04	None	0	0	0	0	0
T/A	rs1196119784	None	0.019	N	0.361	0.072	0.137902524267	gnomAD-4.0.0	4.05955E-06	None	None	None	None	N	None	1.74691E-05	0	None	0	1.13404E-04	None	0	0	2.40978E-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
T/A	0.0668	likely_benign	0.0714	benign	-0.72	Destabilizing	0.019	N	0.361	neutral	N	0.474351517	None	None	N
T/C	0.2285	likely_benign	0.2331	benign	-0.429	Destabilizing	0.667	D	0.528	neutral	None	None	None	None	N
T/D	0.3147	likely_benign	0.3378	benign	-0.461	Destabilizing	0.055	N	0.448	neutral	None	None	None	None	N
T/E	0.1937	likely_benign	0.2068	benign	-0.416	Destabilizing	None	N	0.306	neutral	None	None	None	None	N
T/F	0.2095	likely_benign	0.2303	benign	-0.541	Destabilizing	0.497	N	0.657	neutral	None	None	None	None	N
T/G	0.1648	likely_benign	0.1796	benign	-1.037	Destabilizing	0.055	N	0.449	neutral	None	None	None	None	N
T/H	0.2419	likely_benign	0.2475	benign	-1.342	Destabilizing	0.667	D	0.593	neutral	None	None	None	None	N
T/I	0.0949	likely_benign	0.1032	benign	0.048	Stabilizing	0.042	N	0.359	neutral	N	0.511445681	None	None	N
T/K	0.1601	likely_benign	0.1652	benign	-0.896	Destabilizing	0.055	N	0.429	neutral	None	None	None	None	N
T/L	0.0818	likely_benign	0.0817	benign	0.048	Stabilizing	None	N	0.289	neutral	None	None	None	None	N
T/M	0.0812	likely_benign	0.0824	benign	0.208	Stabilizing	0.497	N	0.537	neutral	None	None	None	None	N
T/N	0.1223	likely_benign	0.1298	benign	-0.897	Destabilizing	0.096	N	0.447	neutral	N	0.505925218	None	None	N
T/P	0.3802	ambiguous	0.39	ambiguous	-0.174	Destabilizing	0.301	N	0.537	neutral	N	0.457189909	None	None	N
T/Q	0.1693	likely_benign	0.1719	benign	-0.923	Destabilizing	0.011	N	0.33	neutral	None	None	None	None	N
T/R	0.1374	likely_benign	0.1378	benign	-0.787	Destabilizing	0.22	N	0.508	neutral	None	None	None	None	N
T/S	0.0881	likely_benign	0.0945	benign	-1.113	Destabilizing	None	N	0.275	neutral	N	0.432408894	None	None	N
T/V	0.0755	likely_benign	0.0799	benign	-0.174	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
T/W	0.5681	likely_pathogenic	0.5714	pathogenic	-0.575	Destabilizing	0.958	D	0.631	neutral	None	None	None	None	N
T/Y	0.2671	likely_benign	0.2788	benign	-0.34	Destabilizing	0.667	D	0.665	neutral	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.