TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7224	21895;21896;21897	chr2:178723430;178723429;178723428	chr2:179588157;179588156;179588155
N2AB	6907	20944;20945;20946	chr2:178723430;178723429;178723428	chr2:179588157;179588156;179588155
N2A	5980	18163;18164;18165	chr2:178723430;178723429;178723428	chr2:179588157;179588156;179588155
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-56
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0633
• 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/F	rs747568681	-1.355	1.0	D	0.835	0.578	0.639540451167	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.31E-05	None	0	0	0
L/F	rs747568681	-1.355	1.0	D	0.835	0.578	0.639540451167	gnomAD-4.0.0	1.59592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43947E-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	0.8749	likely_pathogenic	0.8953	pathogenic	-2.606	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/C	0.8511	likely_pathogenic	0.8701	pathogenic	-1.865	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/D	0.9979	likely_pathogenic	0.9986	pathogenic	-2.916	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/E	0.9886	likely_pathogenic	0.9914	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/F	0.4925	ambiguous	0.6049	pathogenic	-1.561	Destabilizing	1.0	D	0.835	deleterious	D	0.5244156	None	None	N
L/G	0.9724	likely_pathogenic	0.9783	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/H	0.9598	likely_pathogenic	0.9723	pathogenic	-2.891	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.55761237	None	None	N
L/I	0.1645	likely_benign	0.1741	benign	-0.703	Destabilizing	0.999	D	0.55	neutral	N	0.50219306	None	None	N
L/K	0.9842	likely_pathogenic	0.988	pathogenic	-1.992	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/M	0.3164	likely_benign	0.3663	ambiguous	-0.791	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/N	0.9843	likely_pathogenic	0.9877	pathogenic	-2.652	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/P	0.9877	likely_pathogenic	0.9905	pathogenic	-1.325	Destabilizing	1.0	D	0.893	deleterious	D	0.55761237	None	None	N
L/Q	0.9502	likely_pathogenic	0.9611	pathogenic	-2.278	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/R	0.9561	likely_pathogenic	0.9646	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.55761237	None	None	N
L/S	0.97	likely_pathogenic	0.979	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/T	0.9181	likely_pathogenic	0.9339	pathogenic	-2.827	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/V	0.1817	likely_benign	0.186	benign	-1.325	Destabilizing	0.999	D	0.545	neutral	N	0.485108628	None	None	N
L/W	0.9137	likely_pathogenic	0.9458	pathogenic	-1.934	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/Y	0.8962	likely_pathogenic	0.9276	pathogenic	-1.668	Destabilizing	1.0	D	0.875	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.