TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6614	20065;20066;20067	chr2:178727738;178727737;178727736	chr2:179592465;179592464;179592463
N2AB	6297	19114;19115;19116	chr2:178727738;178727737;178727736	chr2:179592465;179592464;179592463
N2A	5370	16333;16334;16335	chr2:178727738;178727737;178727736	chr2:179592465;179592464;179592463
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-50
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1813
• 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
L/I	rs758885175	-0.538	0.884	N	0.364	0.274	0.581442141994	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/I	rs758885175	-0.538	0.884	N	0.364	0.274	0.581442141994	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	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	0.5823	likely_pathogenic	0.6104	pathogenic	-2.117	Highly Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
L/C	0.8227	likely_pathogenic	0.8546	pathogenic	-1.205	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
L/D	0.9659	likely_pathogenic	0.9646	pathogenic	-2.205	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/E	0.8027	likely_pathogenic	0.8027	pathogenic	-1.989	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/F	0.3105	likely_benign	0.3616	ambiguous	-1.257	Destabilizing	0.999	D	0.738	prob.delet.	N	0.509999826	None	None	N
L/G	0.9075	likely_pathogenic	0.9129	pathogenic	-2.618	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/H	0.7311	likely_pathogenic	0.7483	pathogenic	-1.876	Destabilizing	1.0	D	0.869	deleterious	D	0.557755679	None	None	N
L/I	0.0876	likely_benign	0.1004	benign	-0.685	Destabilizing	0.884	D	0.364	neutral	N	0.503008783	None	None	N
L/K	0.7786	likely_pathogenic	0.7735	pathogenic	-1.548	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/M	0.1506	likely_benign	0.1639	benign	-0.536	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/N	0.8772	likely_pathogenic	0.8777	pathogenic	-1.894	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/P	0.9012	likely_pathogenic	0.909	pathogenic	-1.142	Destabilizing	1.0	D	0.887	deleterious	D	0.5459813	None	None	N
L/Q	0.5933	likely_pathogenic	0.5926	pathogenic	-1.772	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/R	0.6822	likely_pathogenic	0.6758	pathogenic	-1.279	Destabilizing	1.0	D	0.876	deleterious	D	0.5459813	None	None	N
L/S	0.8239	likely_pathogenic	0.8324	pathogenic	-2.562	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/T	0.5481	ambiguous	0.5685	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/V	0.1141	likely_benign	0.135	benign	-1.142	Destabilizing	0.981	D	0.532	neutral	D	0.537526788	None	None	N
L/W	0.5912	likely_pathogenic	0.6262	pathogenic	-1.577	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/Y	0.7041	likely_pathogenic	0.7443	pathogenic	-1.236	Destabilizing	1.0	D	0.84	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.