TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26774	80545;80546;80547	chr2:178565812;178565811;178565810	chr2:179430539;179430538;179430537
N2AB	25133	75622;75623;75624	chr2:178565812;178565811;178565810	chr2:179430539;179430538;179430537
N2A	24206	72841;72842;72843	chr2:178565812;178565811;178565810	chr2:179430539;179430538;179430537
N2B	17709	53350;53351;53352	chr2:178565812;178565811;178565810	chr2:179430539;179430538;179430537
Novex-1	17834	53725;53726;53727	chr2:178565812;178565811;178565810	chr2:179430539;179430538;179430537
Novex-2	17901	53926;53927;53928	chr2:178565812;178565811;178565810	chr2:179430539;179430538;179430537
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-82
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.2063
• 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
A/V	rs1272733739	-0.207	0.813	N	0.549	0.361	0.372268306217	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
A/V	rs1272733739	-0.207	0.813	N	0.549	0.361	0.372268306217	gnomAD-4.0.0	6.36643E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	8.31901E-05	None	0	0	0	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
A/C	0.5354	ambiguous	0.5765	pathogenic	-0.649	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	N
A/D	0.818	likely_pathogenic	0.8042	pathogenic	-0.249	Destabilizing	0.682	D	0.771	deleterious	N	0.486724335	None	None	N
A/E	0.6951	likely_pathogenic	0.6656	pathogenic	-0.332	Destabilizing	0.74	D	0.689	prob.delet.	None	None	None	None	N
A/F	0.6618	likely_pathogenic	0.6645	pathogenic	-0.758	Destabilizing	0.984	D	0.853	deleterious	None	None	None	None	N
A/G	0.191	likely_benign	0.1802	benign	-0.687	Destabilizing	0.469	N	0.428	neutral	N	0.500605117	None	None	N
A/H	0.8217	likely_pathogenic	0.8253	pathogenic	-0.725	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
A/I	0.4879	ambiguous	0.5006	ambiguous	-0.204	Destabilizing	0.953	D	0.711	prob.delet.	None	None	None	None	N
A/K	0.8718	likely_pathogenic	0.8617	pathogenic	-0.767	Destabilizing	0.74	D	0.687	prob.delet.	None	None	None	None	N
A/L	0.436	ambiguous	0.4569	ambiguous	-0.204	Destabilizing	0.74	D	0.665	prob.neutral	None	None	None	None	N
A/M	0.424	ambiguous	0.4344	ambiguous	-0.249	Destabilizing	0.996	D	0.697	prob.delet.	None	None	None	None	N
A/N	0.6088	likely_pathogenic	0.6157	pathogenic	-0.427	Destabilizing	0.909	D	0.737	deleterious	None	None	None	None	N
A/P	0.154	likely_benign	0.1617	benign	-0.265	Destabilizing	0.003	N	0.318	neutral	N	0.414679643	None	None	N
A/Q	0.688	likely_pathogenic	0.6887	pathogenic	-0.602	Destabilizing	0.953	D	0.706	prob.delet.	None	None	None	None	N
A/R	0.8262	likely_pathogenic	0.81	pathogenic	-0.417	Destabilizing	0.953	D	0.713	prob.delet.	None	None	None	None	N
A/S	0.1331	likely_benign	0.1308	benign	-0.782	Destabilizing	0.034	N	0.21	neutral	N	0.4303211	None	None	N
A/T	0.202	likely_benign	0.2023	benign	-0.766	Destabilizing	0.518	D	0.495	neutral	N	0.521556392	None	None	N
A/V	0.2527	likely_benign	0.2618	benign	-0.265	Destabilizing	0.813	D	0.549	neutral	N	0.470740783	None	None	N
A/W	0.9228	likely_pathogenic	0.9257	pathogenic	-1.006	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
A/Y	0.7807	likely_pathogenic	0.783	pathogenic	-0.615	Destabilizing	0.984	D	0.853	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.