TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31846	95761;95762;95763	chr2:178545574;178545573;178545572	chr2:179410301;179410300;179410299
N2AB	30205	90838;90839;90840	chr2:178545574;178545573;178545572	chr2:179410301;179410300;179410299
N2A	29278	88057;88058;88059	chr2:178545574;178545573;178545572	chr2:179410301;179410300;179410299
N2B	22781	68566;68567;68568	chr2:178545574;178545573;178545572	chr2:179410301;179410300;179410299
Novex-1	22906	68941;68942;68943	chr2:178545574;178545573;178545572	chr2:179410301;179410300;179410299
Novex-2	22973	69142;69143;69144	chr2:178545574;178545573;178545572	chr2:179410301;179410300;179410299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-120
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1778
• 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
K/R	rs759982252	-1.344	0.999	N	0.723	0.3	None	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	1.93748E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs759982252	-1.344	0.999	N	0.723	0.3	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs759982252	-1.344	0.999	N	0.723	0.3	None	gnomAD-4.0.0	8.96817E-06	None	None	None	None	N	None	1.18403E-04	0	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
K/A	0.9702	likely_pathogenic	0.9695	pathogenic	-1.39	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
K/C	0.8909	likely_pathogenic	0.8943	pathogenic	-1.45	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
K/D	0.9986	likely_pathogenic	0.9985	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/E	0.9503	likely_pathogenic	0.9503	pathogenic	-1.736	Destabilizing	0.999	D	0.747	deleterious	N	0.497057136	None	None	N
K/F	0.9758	likely_pathogenic	0.9709	pathogenic	-0.614	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
K/G	0.9824	likely_pathogenic	0.9846	pathogenic	-1.902	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/H	0.8178	likely_pathogenic	0.8003	pathogenic	-1.66	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/I	0.8967	likely_pathogenic	0.8656	pathogenic	0.074	Stabilizing	1.0	D	0.879	deleterious	N	0.47511454	None	None	N
K/L	0.8734	likely_pathogenic	0.844	pathogenic	0.074	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/M	0.7105	likely_pathogenic	0.6727	pathogenic	-0.288	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/N	0.9935	likely_pathogenic	0.9929	pathogenic	-1.924	Destabilizing	1.0	D	0.826	deleterious	D	0.526517697	None	None	N
K/P	0.9993	likely_pathogenic	0.9993	pathogenic	-0.395	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/Q	0.5836	likely_pathogenic	0.5857	pathogenic	-1.501	Destabilizing	1.0	D	0.839	deleterious	N	0.484384158	None	None	N
K/R	0.1104	likely_benign	0.0995	benign	-0.887	Destabilizing	0.999	D	0.723	prob.delet.	N	0.441847602	None	None	N
K/S	0.9836	likely_pathogenic	0.9833	pathogenic	-2.442	Highly Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/T	0.9219	likely_pathogenic	0.9182	pathogenic	-1.834	Destabilizing	1.0	D	0.83	deleterious	N	0.507145994	None	None	N
K/V	0.8535	likely_pathogenic	0.8218	pathogenic	-0.395	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
K/W	0.9664	likely_pathogenic	0.9557	pathogenic	-0.682	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/Y	0.9216	likely_pathogenic	0.904	pathogenic	-0.333	Destabilizing	1.0	D	0.853	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.