TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7342	22249;22250;22251	chr2:178722875;178722874;178722873	chr2:179587602;179587601;179587600
N2AB	7025	21298;21299;21300	chr2:178722875;178722874;178722873	chr2:179587602;179587601;179587600
N2A	6098	18517;18518;18519	chr2:178722875;178722874;178722873	chr2:179587602;179587601;179587600
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: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-58
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1853
• 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/V	rs1243764269	-0.962	0.992	D	0.687	0.564	0.622959606287	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
L/V	rs1243764269	-0.962	0.992	D	0.687	0.564	0.622959606287	gnomAD-4.0.0	4.77925E-06	None	None	None	None	N	None	0	6.87096E-05	None	0	0	None	0	0	0	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	0.8396	likely_pathogenic	0.9459	pathogenic	-1.803	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/C	0.8576	likely_pathogenic	0.9496	pathogenic	-1.247	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/D	0.9959	likely_pathogenic	0.9993	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/E	0.9698	likely_pathogenic	0.9946	pathogenic	-2.33	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/F	0.1284	likely_benign	0.2284	benign	-1.138	Destabilizing	0.907	D	0.49	neutral	D	0.535502417	None	None	N
L/G	0.9632	likely_pathogenic	0.9916	pathogenic	-2.297	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/H	0.8592	likely_pathogenic	0.9675	pathogenic	-2.391	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/I	0.1377	likely_benign	0.1909	benign	-0.309	Destabilizing	0.99	D	0.671	neutral	D	0.54332022	None	None	N
L/K	0.9325	likely_pathogenic	0.986	pathogenic	-1.366	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/M	0.1941	likely_benign	0.2585	benign	-0.742	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
L/N	0.9771	likely_pathogenic	0.9954	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/P	0.9856	likely_pathogenic	0.9973	pathogenic	-0.801	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/Q	0.8324	likely_pathogenic	0.9624	pathogenic	-1.648	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/R	0.8593	likely_pathogenic	0.9709	pathogenic	-1.815	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/S	0.9375	likely_pathogenic	0.9873	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.636811135	None	None	N
L/T	0.8861	likely_pathogenic	0.9697	pathogenic	-1.96	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/V	0.1876	likely_benign	0.2864	benign	-0.801	Destabilizing	0.992	D	0.687	prob.neutral	D	0.574510646	None	None	N
L/W	0.5493	ambiguous	0.8319	pathogenic	-1.433	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/Y	0.6881	likely_pathogenic	0.8786	pathogenic	-1.262	Destabilizing	0.997	D	0.827	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.