TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4973	15142;15143;15144	chr2:178735529;178735528;178735527	chr2:179600256;179600255;179600254
N2AB	4656	14191;14192;14193	chr2:178735529;178735528;178735527	chr2:179600256;179600255;179600254
N2A	3729	11410;11411;11412	chr2:178735529;178735528;178735527	chr2:179600256;179600255;179600254
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-32
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1409
• 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/T	None	None	0.014	D	0.452	0.135	0.137902524267	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.482	ambiguous	0.5598	ambiguous	-1.062	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
A/D	0.556	ambiguous	0.645	pathogenic	-1.215	Destabilizing	0.942	D	0.785	deleterious	D	0.7699434000000001	None	None	N
A/E	0.5543	ambiguous	0.6631	pathogenic	-1.199	Destabilizing	0.956	D	0.783	deleterious	None	None	None	None	N
A/F	0.5618	ambiguous	0.687	pathogenic	-0.983	Destabilizing	0.956	D	0.795	deleterious	None	None	None	None	N
A/G	0.1373	likely_benign	0.1475	benign	-1.284	Destabilizing	0.698	D	0.585	neutral	D	0.52321945	None	None	N
A/H	0.7519	likely_pathogenic	0.8203	pathogenic	-1.483	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
A/I	0.3202	likely_benign	0.4766	ambiguous	-0.242	Destabilizing	0.915	D	0.784	deleterious	None	None	None	None	N
A/K	0.714	likely_pathogenic	0.797	pathogenic	-1.163	Destabilizing	0.86	D	0.768	deleterious	None	None	None	None	N
A/L	0.2972	likely_benign	0.4206	ambiguous	-0.242	Destabilizing	0.514	D	0.687	prob.neutral	None	None	None	None	N
A/M	0.3072	likely_benign	0.4121	ambiguous	-0.282	Destabilizing	0.559	D	0.669	neutral	None	None	None	None	N
A/N	0.4477	ambiguous	0.5621	ambiguous	-0.984	Destabilizing	0.956	D	0.783	deleterious	None	None	None	None	N
A/P	0.8712	likely_pathogenic	0.9193	pathogenic	-0.441	Destabilizing	0.97	D	0.788	deleterious	D	0.733867162	None	None	N
A/Q	0.6254	likely_pathogenic	0.7071	pathogenic	-1.07	Destabilizing	0.978	D	0.799	deleterious	None	None	None	None	N
A/R	0.6604	likely_pathogenic	0.7398	pathogenic	-0.936	Destabilizing	0.956	D	0.795	deleterious	None	None	None	None	N
A/S	0.0999	likely_benign	0.1051	benign	-1.415	Destabilizing	0.058	N	0.308	neutral	D	0.590506967	None	None	N
A/T	0.0835	likely_benign	0.0977	benign	-1.289	Destabilizing	0.014	N	0.452	neutral	D	0.566074726	None	None	N
A/V	0.1539	likely_benign	0.2147	benign	-0.441	Destabilizing	0.698	D	0.599	neutral	N	0.51480646	None	None	N
A/W	0.9024	likely_pathogenic	0.9405	pathogenic	-1.387	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
A/Y	0.7014	likely_pathogenic	0.7949	pathogenic	-0.94	Destabilizing	0.978	D	0.818	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.