TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14822	44689;44690;44691	chr2:178625357;178625356;178625355	chr2:179490084;179490083;179490082
N2AB	13181	39766;39767;39768	chr2:178625357;178625356;178625355	chr2:179490084;179490083;179490082
N2A	12254	36985;36986;36987	chr2:178625357;178625356;178625355	chr2:179490084;179490083;179490082
N2B	5757	17494;17495;17496	chr2:178625357;178625356;178625355	chr2:179490084;179490083;179490082
Novex-1	5882	17869;17870;17871	chr2:178625357;178625356;178625355	chr2:179490084;179490083;179490082
Novex-2	5949	18070;18071;18072	chr2:178625357;178625356;178625355	chr2:179490084;179490083;179490082
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: Ig-99
• Domain position: 58
• Structural Position: 140
• Q(SASA): 0.1819
• 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/R	rs1235710023	-1.253	0.999	D	0.82	0.692	0.85728530589	gnomAD-2.1.1	4.26E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.23E-06	0
L/R	rs1235710023	-1.253	0.999	D	0.82	0.692	0.85728530589	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/R	rs1235710023	-1.253	0.999	D	0.82	0.692	0.85728530589	gnomAD-4.0.0	3.92008E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.28116E-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	0.8858	likely_pathogenic	0.8969	pathogenic	-2.962	Highly Destabilizing	0.992	D	0.671	neutral	None	None	None	None	N
L/C	0.8398	likely_pathogenic	0.8539	pathogenic	-2.628	Highly Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
L/D	0.995	likely_pathogenic	0.9953	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/E	0.9564	likely_pathogenic	0.961	pathogenic	-2.97	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/F	0.2633	likely_benign	0.2804	benign	-1.824	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/G	0.9788	likely_pathogenic	0.978	pathogenic	-3.586	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/H	0.8447	likely_pathogenic	0.8603	pathogenic	-3.047	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/I	0.0887	likely_benign	0.0927	benign	-1.118	Destabilizing	0.611	D	0.356	neutral	None	None	None	None	N
L/K	0.8828	likely_pathogenic	0.8896	pathogenic	-2.382	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/M	0.1846	likely_benign	0.1969	benign	-1.314	Destabilizing	0.998	D	0.677	prob.neutral	D	0.558424357	None	None	N
L/N	0.9719	likely_pathogenic	0.9737	pathogenic	-2.928	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/P	0.9915	likely_pathogenic	0.9901	pathogenic	-1.718	Destabilizing	0.999	D	0.84	deleterious	D	0.675597966	None	None	N
L/Q	0.8121	likely_pathogenic	0.8254	pathogenic	-2.668	Highly Destabilizing	0.999	D	0.825	deleterious	D	0.675597966	None	None	N
L/R	0.8163	likely_pathogenic	0.8237	pathogenic	-2.209	Highly Destabilizing	0.999	D	0.82	deleterious	D	0.675597966	None	None	N
L/S	0.9487	likely_pathogenic	0.9516	pathogenic	-3.702	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
L/T	0.8778	likely_pathogenic	0.8896	pathogenic	-3.235	Highly Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
L/V	0.1322	likely_benign	0.1461	benign	-1.718	Destabilizing	0.543	D	0.34	neutral	N	0.509677941	None	None	N
L/W	0.6173	likely_pathogenic	0.6035	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/Y	0.7191	likely_pathogenic	0.726	pathogenic	-1.943	Destabilizing	1.0	D	0.745	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.