TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10045	30358;30359;30360	chr2:178704237;178704236;178704235	chr2:179568964;179568963;179568962
N2AB	9728	29407;29408;29409	chr2:178704237;178704236;178704235	chr2:179568964;179568963;179568962
N2A	8801	26626;26627;26628	chr2:178704237;178704236;178704235	chr2:179568964;179568963;179568962
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-85
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0786
• 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/W	rs776484795	-1.715	1.0	None	0.843	0.765	0.878366613624	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/W	rs776484795	-1.715	1.0	None	0.843	0.765	0.878366613624	gnomAD-4.0.0	3.04479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61477E-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	0.9693	likely_pathogenic	0.9859	pathogenic	-2.734	Highly Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
L/C	0.9551	likely_pathogenic	0.9846	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-3.565	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/E	0.9972	likely_pathogenic	0.9981	pathogenic	-3.249	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/F	0.6649	likely_pathogenic	0.8276	pathogenic	-1.613	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
L/G	0.9935	likely_pathogenic	0.9963	pathogenic	-3.343	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/H	0.9904	likely_pathogenic	0.9951	pathogenic	-3.091	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/I	0.3389	likely_benign	0.5204	ambiguous	-0.901	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
L/K	0.9937	likely_pathogenic	0.9952	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/M	0.3576	ambiguous	0.5129	ambiguous	-1.146	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/N	0.9974	likely_pathogenic	0.998	pathogenic	-2.823	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/P	0.9992	likely_pathogenic	0.9997	pathogenic	-1.503	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/Q	0.9869	likely_pathogenic	0.9923	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/R	0.9877	likely_pathogenic	0.9921	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/S	0.9974	likely_pathogenic	0.999	pathogenic	-3.385	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/T	0.9893	likely_pathogenic	0.9949	pathogenic	-2.906	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
L/V	0.4408	ambiguous	0.6661	pathogenic	-1.503	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
L/W	0.9487	likely_pathogenic	0.9814	pathogenic	-2.1	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/Y	0.9585	likely_pathogenic	0.9779	pathogenic	-1.875	Destabilizing	1.0	D	0.832	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.