TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17288	52087;52088;52089	chr2:178609448;178609447;178609446	chr2:179474175;179474174;179474173
N2AB	15647	47164;47165;47166	chr2:178609448;178609447;178609446	chr2:179474175;179474174;179474173
N2A	14720	44383;44384;44385	chr2:178609448;178609447;178609446	chr2:179474175;179474174;179474173
N2B	8223	24892;24893;24894	chr2:178609448;178609447;178609446	chr2:179474175;179474174;179474173
Novex-1	8348	25267;25268;25269	chr2:178609448;178609447;178609446	chr2:179474175;179474174;179474173
Novex-2	8415	25468;25469;25470	chr2:178609448;178609447;178609446	chr2:179474175;179474174;179474173
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-112
• Domain position: 38
• Structural Position: 58
• Q(SASA): 0.0843
• 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/T	rs1366192608	None	0.939	N	0.808	0.476	0.717526509295	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
I/T	rs1366192608	None	0.939	N	0.808	0.476	0.717526509295	gnomAD-4.0.0	1.02714E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25993E-05	1.16012E-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
I/A	0.4323	ambiguous	0.4435	ambiguous	-2.114	Highly Destabilizing	0.91	D	0.719	prob.delet.	None	None	None	None	N
I/C	0.799	likely_pathogenic	0.8236	pathogenic	-1.534	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
I/D	0.9233	likely_pathogenic	0.9175	pathogenic	-2.305	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
I/E	0.8405	likely_pathogenic	0.8264	pathogenic	-2.089	Highly Destabilizing	0.993	D	0.855	deleterious	None	None	None	None	N
I/F	0.2134	likely_benign	0.2225	benign	-1.243	Destabilizing	0.991	D	0.74	deleterious	D	0.524808207	None	None	N
I/G	0.8631	likely_pathogenic	0.87	pathogenic	-2.594	Highly Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
I/H	0.8206	likely_pathogenic	0.8241	pathogenic	-1.798	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
I/K	0.8125	likely_pathogenic	0.8033	pathogenic	-1.773	Destabilizing	0.993	D	0.855	deleterious	None	None	None	None	N
I/L	0.1247	likely_benign	0.1348	benign	-0.741	Destabilizing	0.58	D	0.452	neutral	N	0.473987024	None	None	N
I/M	0.1415	likely_benign	0.154	benign	-0.743	Destabilizing	0.991	D	0.773	deleterious	N	0.493813993	None	None	N
I/N	0.7546	likely_pathogenic	0.7454	pathogenic	-2.215	Highly Destabilizing	0.997	D	0.87	deleterious	N	0.521579487	None	None	N
I/P	0.8282	likely_pathogenic	0.8365	pathogenic	-1.179	Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
I/Q	0.7916	likely_pathogenic	0.7921	pathogenic	-2.058	Highly Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
I/R	0.7126	likely_pathogenic	0.7008	pathogenic	-1.521	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
I/S	0.6375	likely_pathogenic	0.6414	pathogenic	-2.836	Highly Destabilizing	0.991	D	0.855	deleterious	N	0.521072508	None	None	N
I/T	0.3462	ambiguous	0.3623	ambiguous	-2.468	Highly Destabilizing	0.939	D	0.808	deleterious	N	0.518284123	None	None	N
I/V	0.0882	likely_benign	0.0962	benign	-1.179	Destabilizing	0.02	N	0.183	neutral	N	0.480187851	None	None	N
I/W	0.8367	likely_pathogenic	0.8575	pathogenic	-1.497	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
I/Y	0.6755	likely_pathogenic	0.6711	pathogenic	-1.206	Destabilizing	0.998	D	0.826	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.