TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23111	69556;69557;69558	chr2:178577004;178577003;178577002	chr2:179441731;179441730;179441729
N2AB	21470	64633;64634;64635	chr2:178577004;178577003;178577002	chr2:179441731;179441730;179441729
N2A	20543	61852;61853;61854	chr2:178577004;178577003;178577002	chr2:179441731;179441730;179441729
N2B	14046	42361;42362;42363	chr2:178577004;178577003;178577002	chr2:179441731;179441730;179441729
Novex-1	14171	42736;42737;42738	chr2:178577004;178577003;178577002	chr2:179441731;179441730;179441729
Novex-2	14238	42937;42938;42939	chr2:178577004;178577003;178577002	chr2:179441731;179441730;179441729
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: Fn3-55
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.0735
• 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/V	rs1398776954	-1.53	None	N	0.207	0.184	0.158396225186	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/V	rs1398776954	-1.53	None	N	0.207	0.184	0.158396225186	gnomAD-4.0.0	5.47461E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.1969E-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
I/A	0.4344	ambiguous	0.3581	ambiguous	-2.718	Highly Destabilizing	0.072	N	0.698	prob.neutral	None	None	None	None	N
I/C	0.5659	likely_pathogenic	0.5102	ambiguous	-1.753	Destabilizing	0.909	D	0.729	prob.delet.	None	None	None	None	N
I/D	0.8333	likely_pathogenic	0.7951	pathogenic	-3.161	Highly Destabilizing	0.726	D	0.815	deleterious	None	None	None	None	N
I/E	0.6237	likely_pathogenic	0.5753	pathogenic	-2.907	Highly Destabilizing	0.726	D	0.797	deleterious	None	None	None	None	N
I/F	0.2181	likely_benign	0.1937	benign	-1.529	Destabilizing	0.331	N	0.721	prob.delet.	N	0.505146932	None	None	N
I/G	0.7408	likely_pathogenic	0.6735	pathogenic	-3.245	Highly Destabilizing	0.726	D	0.78	deleterious	None	None	None	None	N
I/H	0.5727	likely_pathogenic	0.5234	ambiguous	-2.746	Highly Destabilizing	0.968	D	0.809	deleterious	None	None	None	None	N
I/K	0.5763	likely_pathogenic	0.5425	ambiguous	-1.906	Destabilizing	0.726	D	0.787	deleterious	None	None	None	None	N
I/L	0.0902	likely_benign	0.077	benign	-1.16	Destabilizing	None	N	0.261	neutral	N	0.481096636	None	None	N
I/M	0.1137	likely_benign	0.0967	benign	-1.206	Destabilizing	0.331	N	0.724	prob.delet.	D	0.523906051	None	None	N
I/N	0.4009	ambiguous	0.3594	ambiguous	-2.342	Highly Destabilizing	0.859	D	0.819	deleterious	N	0.501623837	None	None	N
I/P	0.9828	likely_pathogenic	0.9803	pathogenic	-1.667	Destabilizing	0.726	D	0.813	deleterious	None	None	None	None	N
I/Q	0.4598	ambiguous	0.4127	ambiguous	-2.139	Highly Destabilizing	0.89	D	0.821	deleterious	None	None	None	None	N
I/R	0.4734	ambiguous	0.4342	ambiguous	-1.727	Destabilizing	0.726	D	0.819	deleterious	None	None	None	None	N
I/S	0.3481	ambiguous	0.2985	benign	-2.938	Highly Destabilizing	0.497	N	0.743	deleterious	N	0.507915091	None	None	N
I/T	0.2504	likely_benign	0.2064	benign	-2.554	Highly Destabilizing	0.124	N	0.747	deleterious	N	0.468625985	None	None	N
I/V	0.069	likely_benign	0.0623	benign	-1.667	Destabilizing	None	N	0.207	neutral	N	0.507088372	None	None	N
I/W	0.8151	likely_pathogenic	0.7949	pathogenic	-1.949	Destabilizing	0.968	D	0.798	deleterious	None	None	None	None	N
I/Y	0.5334	ambiguous	0.5197	ambiguous	-1.728	Destabilizing	0.726	D	0.761	deleterious	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.