TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5787	17584;17585;17586	chr2:178731407;178731406;178731405	chr2:179596134;179596133;179596132
N2AB	5470	16633;16634;16635	chr2:178731407;178731406;178731405	chr2:179596134;179596133;179596132
N2A	4543	13852;13853;13854	chr2:178731407;178731406;178731405	chr2:179596134;179596133;179596132
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-41
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0543
• 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/S	rs752558864	-2.694	0.997	D	0.808	0.852	0.898220301615	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.34E-05	0
L/S	rs752558864	-2.694	0.997	D	0.808	0.852	0.898220301615	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/S	rs752558864	-2.694	0.997	D	0.808	0.852	0.898220301615	gnomAD-4.0.0	2.41686E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.13616E-05	0	3.20256E-05

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	0.9206	likely_pathogenic	0.9236	pathogenic	-2.142	Highly Destabilizing	0.983	D	0.747	deleterious	None	None	None	None	N
L/C	0.8482	likely_pathogenic	0.852	pathogenic	-1.361	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-2.944	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
L/E	0.9982	likely_pathogenic	0.9975	pathogenic	-2.642	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
L/F	0.554	ambiguous	0.5975	pathogenic	-1.363	Destabilizing	0.997	D	0.611	neutral	D	0.547209068	None	None	N
L/G	0.9876	likely_pathogenic	0.9857	pathogenic	-2.682	Highly Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
L/H	0.9911	likely_pathogenic	0.9896	pathogenic	-2.66	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/I	0.2238	likely_benign	0.2504	benign	-0.505	Destabilizing	0.437	N	0.392	neutral	None	None	None	None	N
L/K	0.9962	likely_pathogenic	0.9947	pathogenic	-1.59	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
L/M	0.3343	likely_benign	0.4016	ambiguous	-0.792	Destabilizing	0.997	D	0.62	neutral	D	0.529611792	None	None	N
L/N	0.9972	likely_pathogenic	0.9963	pathogenic	-2.339	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9969	pathogenic	-1.045	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
L/Q	0.9875	likely_pathogenic	0.9862	pathogenic	-1.928	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/R	0.9877	likely_pathogenic	0.9836	pathogenic	-1.934	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/S	0.9914	likely_pathogenic	0.9915	pathogenic	-2.719	Highly Destabilizing	0.997	D	0.808	deleterious	D	0.549236984	None	None	N
L/T	0.9746	likely_pathogenic	0.9763	pathogenic	-2.258	Highly Destabilizing	0.983	D	0.763	deleterious	None	None	None	None	N
L/V	0.2498	likely_benign	0.2936	benign	-1.045	Destabilizing	0.37	N	0.427	neutral	D	0.547462557	None	None	N
L/W	0.9682	likely_pathogenic	0.9701	pathogenic	-1.706	Destabilizing	1.0	D	0.83	deleterious	D	0.549236984	None	None	N
L/Y	0.9617	likely_pathogenic	0.9648	pathogenic	-1.511	Destabilizing	0.999	D	0.727	prob.delet.	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.