TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24090	72493;72494;72495	chr2:178573864;178573863;178573862	chr2:179438591;179438590;179438589
N2AB	22449	67570;67571;67572	chr2:178573864;178573863;178573862	chr2:179438591;179438590;179438589
N2A	21522	64789;64790;64791	chr2:178573864;178573863;178573862	chr2:179438591;179438590;179438589
N2B	15025	45298;45299;45300	chr2:178573864;178573863;178573862	chr2:179438591;179438590;179438589
Novex-1	15150	45673;45674;45675	chr2:178573864;178573863;178573862	chr2:179438591;179438590;179438589
Novex-2	15217	45874;45875;45876	chr2:178573864;178573863;178573862	chr2:179438591;179438590;179438589
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: Ig-131
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.343
• 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/E	rs1709122606	None	0.999	N	0.57	0.437	0.426904299391	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	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	0.6666	likely_pathogenic	0.6901	pathogenic	-0.342	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
K/C	0.8895	likely_pathogenic	0.8946	pathogenic	-0.357	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
K/D	0.8879	likely_pathogenic	0.8954	pathogenic	-0.356	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/E	0.4671	ambiguous	0.4975	ambiguous	-0.299	Destabilizing	0.999	D	0.57	neutral	N	0.514164352	None	None	N
K/F	0.9219	likely_pathogenic	0.9232	pathogenic	-0.303	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/G	0.75	likely_pathogenic	0.7675	pathogenic	-0.659	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/H	0.5357	ambiguous	0.5397	ambiguous	-1.124	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	N
K/I	0.5885	likely_pathogenic	0.593	pathogenic	0.454	Stabilizing	1.0	D	0.714	prob.delet.	N	0.48922841	None	None	N
K/L	0.6133	likely_pathogenic	0.6343	pathogenic	0.454	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/M	0.4638	ambiguous	0.4755	ambiguous	0.522	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	N
K/N	0.7901	likely_pathogenic	0.8095	pathogenic	-0.269	Destabilizing	1.0	D	0.666	neutral	N	0.516916656	None	None	N
K/P	0.8854	likely_pathogenic	0.8936	pathogenic	0.219	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/Q	0.2858	likely_benign	0.3018	benign	-0.476	Destabilizing	1.0	D	0.65	neutral	D	0.531960679	None	None	N
K/R	0.0883	likely_benign	0.0926	benign	-0.459	Destabilizing	0.999	D	0.502	neutral	N	0.453366609	None	None	N
K/S	0.7668	likely_pathogenic	0.7872	pathogenic	-0.835	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
K/T	0.3732	ambiguous	0.3893	ambiguous	-0.598	Destabilizing	1.0	D	0.688	prob.neutral	N	0.511625479	None	None	N
K/V	0.5736	likely_pathogenic	0.5825	pathogenic	0.219	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/W	0.8737	likely_pathogenic	0.8785	pathogenic	-0.214	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/Y	0.8289	likely_pathogenic	0.8274	pathogenic	0.121	Stabilizing	1.0	D	0.663	neutral	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.