TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29592	88999;89000;89001	chr2:178554573;178554572;178554571	chr2:179419300;179419299;179419298
N2AB	27951	84076;84077;84078	chr2:178554573;178554572;178554571	chr2:179419300;179419299;179419298
N2A	27024	81295;81296;81297	chr2:178554573;178554572;178554571	chr2:179419300;179419299;179419298
N2B	20527	61804;61805;61806	chr2:178554573;178554572;178554571	chr2:179419300;179419299;179419298
Novex-1	20652	62179;62180;62181	chr2:178554573;178554572;178554571	chr2:179419300;179419299;179419298
Novex-2	20719	62380;62381;62382	chr2:178554573;178554572;178554571	chr2:179419300;179419299;179419298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-103
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2857
• 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
I/F	None	None	0.884	N	0.486	0.178	0.319402600006	gnomAD-4.0.0	1.36835E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79885E-06	0	0
I/L	None	None	0.003	N	0.153	0.091	0.223847106136	gnomAD-4.0.0	6.84173E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
I/V	rs1700602244	None	0.309	N	0.389	0.069	0.332902724076	gnomAD-4.0.0	3.42087E-06	None	None	None	None	N	None	0	0	None	0	1.26027E-04	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
I/A	0.231	likely_benign	0.2515	benign	-1.707	Destabilizing	0.037	N	0.254	neutral	None	None	None	None	N
I/C	0.4991	ambiguous	0.4815	ambiguous	-0.917	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	N
I/D	0.5379	ambiguous	0.6052	pathogenic	-1.484	Destabilizing	0.91	D	0.604	neutral	None	None	None	None	N
I/E	0.429	ambiguous	0.4698	ambiguous	-1.359	Destabilizing	0.91	D	0.604	neutral	None	None	None	None	N
I/F	0.1398	likely_benign	0.1689	benign	-0.963	Destabilizing	0.884	D	0.486	neutral	N	0.464761747	None	None	N
I/G	0.4952	ambiguous	0.5391	ambiguous	-2.124	Highly Destabilizing	0.59	D	0.549	neutral	None	None	None	None	N
I/H	0.3263	likely_benign	0.3565	ambiguous	-1.27	Destabilizing	0.996	D	0.606	neutral	None	None	None	None	N
I/K	0.2959	likely_benign	0.3271	benign	-1.202	Destabilizing	0.91	D	0.598	neutral	None	None	None	None	N
I/L	0.0945	likely_benign	0.1036	benign	-0.574	Destabilizing	0.003	N	0.153	neutral	N	0.460452005	None	None	N
I/M	0.0832	likely_benign	0.0888	benign	-0.465	Destabilizing	0.884	D	0.491	neutral	N	0.454064751	None	None	N
I/N	0.1607	likely_benign	0.1865	benign	-1.333	Destabilizing	0.884	D	0.61	neutral	N	0.40642552	None	None	N
I/P	0.8281	likely_pathogenic	0.8833	pathogenic	-0.925	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	N
I/Q	0.3041	likely_benign	0.3246	benign	-1.341	Destabilizing	0.91	D	0.619	neutral	None	None	None	None	N
I/R	0.2213	likely_benign	0.2581	benign	-0.76	Destabilizing	0.91	D	0.612	neutral	None	None	None	None	N
I/S	0.1729	likely_benign	0.1903	benign	-1.963	Destabilizing	0.028	N	0.419	neutral	N	0.381775004	None	None	N
I/T	0.1503	likely_benign	0.1616	benign	-1.709	Destabilizing	0.521	D	0.444	neutral	N	0.387644971	None	None	N
I/V	0.0711	likely_benign	0.0734	benign	-0.925	Destabilizing	0.309	N	0.389	neutral	N	0.460278647	None	None	N
I/W	0.6916	likely_pathogenic	0.7418	pathogenic	-1.199	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
I/Y	0.4115	ambiguous	0.4432	ambiguous	-0.886	Destabilizing	0.984	D	0.551	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.