TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28710	86353;86354;86355	chr2:178560004;178560003;178560002	chr2:179424731;179424730;179424729
N2AB	27069	81430;81431;81432	chr2:178560004;178560003;178560002	chr2:179424731;179424730;179424729
N2A	26142	78649;78650;78651	chr2:178560004;178560003;178560002	chr2:179424731;179424730;179424729
N2B	19645	59158;59159;59160	chr2:178560004;178560003;178560002	chr2:179424731;179424730;179424729
Novex-1	19770	59533;59534;59535	chr2:178560004;178560003;178560002	chr2:179424731;179424730;179424729
Novex-2	19837	59734;59735;59736	chr2:178560004;178560003;178560002	chr2:179424731;179424730;179424729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-97
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.1456
• 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/C	None	None	0.009	N	0.486	0.3	0.314417295294	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	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	0.7455	likely_pathogenic	0.7237	pathogenic	-2.162	Highly Destabilizing	0.447	N	0.482	neutral	None	None	None	None	N
Y/C	0.1771	likely_benign	0.1805	benign	-1.465	Destabilizing	0.009	N	0.486	neutral	N	0.470269141	None	None	N
Y/D	0.8153	likely_pathogenic	0.7858	pathogenic	-1.404	Destabilizing	0.963	D	0.622	neutral	N	0.513496459	None	None	N
Y/E	0.9011	likely_pathogenic	0.8859	pathogenic	-1.243	Destabilizing	0.972	D	0.563	neutral	None	None	None	None	N
Y/F	0.0817	likely_benign	0.0792	benign	-0.66	Destabilizing	0.002	N	0.155	neutral	N	0.413759711	None	None	N
Y/G	0.7524	likely_pathogenic	0.725	pathogenic	-2.531	Highly Destabilizing	0.617	D	0.592	neutral	None	None	None	None	N
Y/H	0.3078	likely_benign	0.2732	benign	-1.002	Destabilizing	0.963	D	0.468	neutral	N	0.507440663	None	None	N
Y/I	0.5931	likely_pathogenic	0.5709	pathogenic	-1.003	Destabilizing	0.447	N	0.455	neutral	None	None	None	None	N
Y/K	0.8455	likely_pathogenic	0.8278	pathogenic	-1.67	Destabilizing	0.92	D	0.567	neutral	None	None	None	None	N
Y/L	0.5993	likely_pathogenic	0.5668	pathogenic	-1.003	Destabilizing	0.25	N	0.431	neutral	None	None	None	None	N
Y/M	0.6475	likely_pathogenic	0.6434	pathogenic	-0.939	Destabilizing	0.92	D	0.516	neutral	None	None	None	None	N
Y/N	0.5075	ambiguous	0.4772	ambiguous	-2.337	Highly Destabilizing	0.963	D	0.589	neutral	N	0.513242969	None	None	N
Y/P	0.9958	likely_pathogenic	0.995	pathogenic	-1.391	Destabilizing	0.972	D	0.654	neutral	None	None	None	None	N
Y/Q	0.7717	likely_pathogenic	0.7397	pathogenic	-2.057	Highly Destabilizing	0.972	D	0.516	neutral	None	None	None	None	N
Y/R	0.7757	likely_pathogenic	0.7453	pathogenic	-1.49	Destabilizing	0.92	D	0.594	neutral	None	None	None	None	N
Y/S	0.6022	likely_pathogenic	0.5648	pathogenic	-2.82	Highly Destabilizing	0.549	D	0.541	neutral	N	0.494885225	None	None	N
Y/T	0.7567	likely_pathogenic	0.7351	pathogenic	-2.544	Highly Destabilizing	0.617	D	0.561	neutral	None	None	None	None	N
Y/V	0.514	ambiguous	0.5046	ambiguous	-1.391	Destabilizing	0.447	N	0.443	neutral	None	None	None	None	N
Y/W	0.5406	ambiguous	0.5559	ambiguous	-0.158	Destabilizing	0.972	D	0.475	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.