TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25954	78085;78086;78087	chr2:178568272;178568271;178568270	chr2:179432999;179432998;179432997
N2AB	24313	73162;73163;73164	chr2:178568272;178568271;178568270	chr2:179432999;179432998;179432997
N2A	23386	70381;70382;70383	chr2:178568272;178568271;178568270	chr2:179432999;179432998;179432997
N2B	16889	50890;50891;50892	chr2:178568272;178568271;178568270	chr2:179432999;179432998;179432997
Novex-1	17014	51265;51266;51267	chr2:178568272;178568271;178568270	chr2:179432999;179432998;179432997
Novex-2	17081	51466;51467;51468	chr2:178568272;178568271;178568270	chr2:179432999;179432998;179432997
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: Fn3-76
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.7879
• 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/Q	rs776215265	0.212	0.994	N	0.508	0.293	0.233785782151	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/Q	rs776215265	0.212	0.994	N	0.508	0.293	0.233785782151	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
K/A	0.6699	likely_pathogenic	0.6036	pathogenic	0.014	Stabilizing	0.985	D	0.47	neutral	None	None	None	None	N
K/C	0.7896	likely_pathogenic	0.7239	pathogenic	-0.432	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/D	0.8248	likely_pathogenic	0.7814	pathogenic	-0.179	Destabilizing	0.942	D	0.467	neutral	None	None	None	None	N
K/E	0.6528	likely_pathogenic	0.5882	pathogenic	-0.192	Destabilizing	0.961	D	0.479	neutral	N	0.504103995	None	None	N
K/F	0.9425	likely_pathogenic	0.9186	pathogenic	-0.303	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
K/G	0.5817	likely_pathogenic	0.5047	ambiguous	-0.122	Destabilizing	0.97	D	0.449	neutral	None	None	None	None	N
K/H	0.3192	likely_benign	0.2498	benign	-0.215	Destabilizing	0.996	D	0.493	neutral	None	None	None	None	N
K/I	0.8593	likely_pathogenic	0.8142	pathogenic	0.286	Stabilizing	0.998	D	0.599	neutral	N	0.502306921	None	None	N
K/L	0.7559	likely_pathogenic	0.6793	pathogenic	0.286	Stabilizing	0.985	D	0.45	neutral	None	None	None	None	N
K/M	0.6694	likely_pathogenic	0.5942	pathogenic	-0.031	Destabilizing	1.0	D	0.494	neutral	None	None	None	None	N
K/N	0.6233	likely_pathogenic	0.5395	ambiguous	0.045	Stabilizing	0.122	N	0.151	neutral	N	0.421157325	None	None	N
K/P	0.9176	likely_pathogenic	0.9081	pathogenic	0.219	Stabilizing	0.999	D	0.487	neutral	None	None	None	None	N
K/Q	0.2896	likely_benign	0.2391	benign	-0.115	Destabilizing	0.994	D	0.508	neutral	N	0.468945567	None	None	N
K/R	0.0744	likely_benign	0.0669	benign	-0.067	Destabilizing	0.98	D	0.471	neutral	N	0.444922406	None	None	N
K/S	0.6775	likely_pathogenic	0.6072	pathogenic	-0.361	Destabilizing	0.97	D	0.462	neutral	None	None	None	None	N
K/T	0.5562	ambiguous	0.4878	ambiguous	-0.252	Destabilizing	0.961	D	0.474	neutral	N	0.474794917	None	None	N
K/V	0.7817	likely_pathogenic	0.7249	pathogenic	0.219	Stabilizing	0.999	D	0.465	neutral	None	None	None	None	N
K/W	0.898	likely_pathogenic	0.8508	pathogenic	-0.379	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/Y	0.8148	likely_pathogenic	0.7467	pathogenic	-0.026	Destabilizing	0.999	D	0.549	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.