TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28916	86971;86972;86973	chr2:178559386;178559385;178559384	chr2:179424113;179424112;179424111
N2AB	27275	82048;82049;82050	chr2:178559386;178559385;178559384	chr2:179424113;179424112;179424111
N2A	26348	79267;79268;79269	chr2:178559386;178559385;178559384	chr2:179424113;179424112;179424111
N2B	19851	59776;59777;59778	chr2:178559386;178559385;178559384	chr2:179424113;179424112;179424111
Novex-1	19976	60151;60152;60153	chr2:178559386;178559385;178559384	chr2:179424113;179424112;179424111
Novex-2	20043	60352;60353;60354	chr2:178559386;178559385;178559384	chr2:179424113;179424112;179424111
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-98
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.2585
• 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
Y/F	None	None	0.005	N	0.271	0.199	0.408853032482	gnomAD-4.0.0	2.73711E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.93963E-04	0	0	0
Y/H	None	None	0.988	N	0.662	0.421	0.543384585148	gnomAD-4.0.0	6.8428E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99577E-07	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
Y/A	0.8307	likely_pathogenic	0.8137	pathogenic	-2.632	Highly Destabilizing	0.942	D	0.641	neutral	None	None	None	None	N
Y/C	0.2135	likely_benign	0.1942	benign	-1.119	Destabilizing	0.999	D	0.699	prob.neutral	N	0.50316542	None	None	N
Y/D	0.8584	likely_pathogenic	0.8454	pathogenic	-1.797	Destabilizing	0.996	D	0.743	deleterious	N	0.486483814	None	None	N
Y/E	0.9595	likely_pathogenic	0.9528	pathogenic	-1.625	Destabilizing	0.997	D	0.705	prob.neutral	None	None	None	None	N
Y/F	0.1128	likely_benign	0.1094	benign	-0.829	Destabilizing	0.005	N	0.271	neutral	N	0.432785402	None	None	N
Y/G	0.7969	likely_pathogenic	0.7959	pathogenic	-3.006	Highly Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
Y/H	0.3887	ambiguous	0.3723	ambiguous	-1.35	Destabilizing	0.988	D	0.662	neutral	N	0.483886226	None	None	N
Y/I	0.7167	likely_pathogenic	0.7054	pathogenic	-1.427	Destabilizing	0.526	D	0.655	neutral	None	None	None	None	N
Y/K	0.9198	likely_pathogenic	0.9159	pathogenic	-1.315	Destabilizing	0.933	D	0.699	prob.neutral	None	None	None	None	N
Y/L	0.6181	likely_pathogenic	0.6297	pathogenic	-1.427	Destabilizing	0.24	N	0.597	neutral	None	None	None	None	N
Y/M	0.8055	likely_pathogenic	0.8043	pathogenic	-1.136	Destabilizing	0.992	D	0.681	prob.neutral	None	None	None	None	N
Y/N	0.5221	ambiguous	0.5243	ambiguous	-1.795	Destabilizing	0.996	D	0.716	prob.delet.	N	0.461585369	None	None	N
Y/P	0.9935	likely_pathogenic	0.9935	pathogenic	-1.836	Destabilizing	0.997	D	0.75	deleterious	None	None	None	None	N
Y/Q	0.8301	likely_pathogenic	0.8235	pathogenic	-1.649	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
Y/R	0.7798	likely_pathogenic	0.7733	pathogenic	-1.012	Destabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
Y/S	0.5021	ambiguous	0.4819	ambiguous	-2.353	Highly Destabilizing	0.989	D	0.701	prob.neutral	N	0.463566881	None	None	N
Y/T	0.7552	likely_pathogenic	0.7349	pathogenic	-2.079	Highly Destabilizing	0.991	D	0.699	prob.neutral	None	None	None	None	N
Y/V	0.6259	likely_pathogenic	0.6097	pathogenic	-1.836	Destabilizing	0.942	D	0.623	neutral	None	None	None	None	N
Y/W	0.5911	likely_pathogenic	0.5714	pathogenic	-0.104	Destabilizing	0.999	D	0.665	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.