TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29290	88093;88094;88095	chr2:178557394;178557393;178557392	chr2:179422121;179422120;179422119
N2AB	27649	83170;83171;83172	chr2:178557394;178557393;178557392	chr2:179422121;179422120;179422119
N2A	26722	80389;80390;80391	chr2:178557394;178557393;178557392	chr2:179422121;179422120;179422119
N2B	20225	60898;60899;60900	chr2:178557394;178557393;178557392	chr2:179422121;179422120;179422119
Novex-1	20350	61273;61274;61275	chr2:178557394;178557393;178557392	chr2:179422121;179422120;179422119
Novex-2	20417	61474;61475;61476	chr2:178557394;178557393;178557392	chr2:179422121;179422120;179422119
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-101
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.5109
• 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
L/P	None	None	0.106	N	0.519	0.133	0.647776319867	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.56251E-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
L/A	0.0946	likely_benign	0.1003	benign	-0.447	Destabilizing	0.007	N	0.293	neutral	None	None	None	None	I
L/C	0.3028	likely_benign	0.3344	benign	-0.748	Destabilizing	0.628	D	0.4	neutral	None	None	None	None	I
L/D	0.4489	ambiguous	0.4261	ambiguous	-0.251	Destabilizing	0.072	N	0.5	neutral	None	None	None	None	I
L/E	0.2885	likely_benign	0.2626	benign	-0.341	Destabilizing	0.072	N	0.449	neutral	None	None	None	None	I
L/F	0.1042	likely_benign	0.1063	benign	-0.595	Destabilizing	0.072	N	0.316	neutral	None	None	None	None	I
L/G	0.2257	likely_benign	0.2427	benign	-0.552	Destabilizing	0.072	N	0.445	neutral	None	None	None	None	I
L/H	0.1415	likely_benign	0.1579	benign	0.115	Stabilizing	0.628	D	0.455	neutral	None	None	None	None	I
L/I	0.0712	likely_benign	0.0662	benign	-0.29	Destabilizing	None	N	0.158	neutral	None	None	None	None	I
L/K	0.2193	likely_benign	0.2133	benign	-0.327	Destabilizing	0.072	N	0.417	neutral	None	None	None	None	I
L/M	0.0485	likely_benign	0.0573	benign	-0.574	Destabilizing	None	N	0.127	neutral	N	0.46926349	None	None	I
L/N	0.1433	likely_benign	0.1346	benign	-0.185	Destabilizing	0.072	N	0.499	neutral	None	None	None	None	I
L/P	0.4603	ambiguous	0.4646	ambiguous	-0.314	Destabilizing	0.106	N	0.519	neutral	N	0.480576562	None	None	I
L/Q	0.1015	likely_benign	0.1146	benign	-0.365	Destabilizing	0.171	N	0.538	neutral	N	0.456968983	None	None	I
L/R	0.1995	likely_benign	0.1988	benign	0.148	Stabilizing	0.055	N	0.493	neutral	N	0.451504448	None	None	I
L/S	0.1039	likely_benign	0.1179	benign	-0.566	Destabilizing	0.016	N	0.369	neutral	None	None	None	None	I
L/T	0.0786	likely_benign	0.084	benign	-0.556	Destabilizing	None	N	0.162	neutral	None	None	None	None	I
L/V	0.0668	likely_benign	0.0681	benign	-0.314	Destabilizing	0.005	N	0.176	neutral	N	0.439033796	None	None	I
L/W	0.1793	likely_benign	0.2088	benign	-0.615	Destabilizing	0.864	D	0.439	neutral	None	None	None	None	I
L/Y	0.2116	likely_benign	0.2184	benign	-0.38	Destabilizing	0.356	N	0.487	neutral	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.