TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5030	15313;15314;15315	chr2:178734836;178734835;178734834	chr2:179599563;179599562;179599561
N2AB	4713	14362;14363;14364	chr2:178734836;178734835;178734834	chr2:179599563;179599562;179599561
N2A	3786	11581;11582;11583	chr2:178734836;178734835;178734834	chr2:179599563;179599562;179599561
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-33
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.1126
• 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
M/I	rs753772585	-0.734	None	N	0.065	0.098	0.363158594168	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
M/I	rs753772585	-0.734	None	N	0.065	0.098	0.363158594168	gnomAD-4.0.0	8.1197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.63939E-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
M/A	0.5259	ambiguous	0.5088	ambiguous	-2.507	Highly Destabilizing	0.048	N	0.323	neutral	None	None	None	None	N
M/C	0.8488	likely_pathogenic	0.847	pathogenic	-1.775	Destabilizing	0.859	D	0.517	neutral	None	None	None	None	N
M/D	0.9317	likely_pathogenic	0.9181	pathogenic	-1.497	Destabilizing	0.364	N	0.561	neutral	None	None	None	None	N
M/E	0.6841	likely_pathogenic	0.6353	pathogenic	-1.326	Destabilizing	0.364	N	0.485	neutral	None	None	None	None	N
M/F	0.3801	ambiguous	0.3442	ambiguous	-0.986	Destabilizing	0.22	N	0.374	neutral	None	None	None	None	N
M/G	0.7524	likely_pathogenic	0.7323	pathogenic	-2.947	Highly Destabilizing	0.364	N	0.474	neutral	None	None	None	None	N
M/H	0.6559	likely_pathogenic	0.6242	pathogenic	-2.139	Highly Destabilizing	0.859	D	0.534	neutral	None	None	None	None	N
M/I	0.3278	likely_benign	0.31	benign	-1.262	Destabilizing	None	N	0.065	neutral	N	0.461491456	None	None	N
M/K	0.2614	likely_benign	0.2319	benign	-1.358	Destabilizing	0.301	N	0.414	neutral	D	0.541983132	None	None	N
M/L	0.1915	likely_benign	0.1851	benign	-1.262	Destabilizing	None	N	0.059	neutral	N	0.483209648	None	None	N
M/N	0.6346	likely_pathogenic	0.6181	pathogenic	-1.474	Destabilizing	0.364	N	0.541	neutral	None	None	None	None	N
M/P	0.9124	likely_pathogenic	0.8711	pathogenic	-1.658	Destabilizing	0.635	D	0.575	neutral	None	None	None	None	N
M/Q	0.344	ambiguous	0.3213	benign	-1.316	Destabilizing	0.635	D	0.464	neutral	None	None	None	None	N
M/R	0.2813	likely_benign	0.2495	benign	-1.146	Destabilizing	0.301	N	0.528	neutral	N	0.505338044	None	None	N
M/S	0.5171	ambiguous	0.4936	ambiguous	-2.136	Highly Destabilizing	0.055	N	0.366	neutral	None	None	None	None	N
M/T	0.3137	likely_benign	0.3088	benign	-1.844	Destabilizing	0.001	N	0.229	neutral	N	0.512313459	None	None	N
M/V	0.144	likely_benign	0.1312	benign	-1.658	Destabilizing	0.003	N	0.251	neutral	N	0.492143638	None	None	N
M/W	0.7136	likely_pathogenic	0.6475	pathogenic	-1.093	Destabilizing	0.958	D	0.499	neutral	None	None	None	None	N
M/Y	0.6393	likely_pathogenic	0.5784	pathogenic	-1.172	Destabilizing	0.667	D	0.568	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.