TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30991	93196;93197;93198	chr2:178548655;178548654;178548653	chr2:179413382;179413381;179413380
N2AB	29350	88273;88274;88275	chr2:178548655;178548654;178548653	chr2:179413382;179413381;179413380
N2A	28423	85492;85493;85494	chr2:178548655;178548654;178548653	chr2:179413382;179413381;179413380
N2B	21926	66001;66002;66003	chr2:178548655;178548654;178548653	chr2:179413382;179413381;179413380
Novex-1	22051	66376;66377;66378	chr2:178548655;178548654;178548653	chr2:179413382;179413381;179413380
Novex-2	22118	66577;66578;66579	chr2:178548655;178548654;178548653	chr2:179413382;179413381;179413380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-150
• Domain position: 65
• Structural Position: 151
• Q(SASA): 0.2875
• 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
A/V	None	None	0.992	N	0.49	0.493	0.604839314244	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
A/C	0.5937	likely_pathogenic	0.5608	ambiguous	-0.929	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/D	0.8958	likely_pathogenic	0.8736	pathogenic	-0.93	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/E	0.8048	likely_pathogenic	0.7797	pathogenic	-1.015	Destabilizing	1.0	D	0.851	deleterious	N	0.513932279	None	None	N
A/F	0.6856	likely_pathogenic	0.6381	pathogenic	-1.125	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
A/G	0.2293	likely_benign	0.2061	benign	-1.023	Destabilizing	0.998	D	0.508	neutral	N	0.488481168	None	None	N
A/H	0.8186	likely_pathogenic	0.7976	pathogenic	-1.072	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/I	0.6618	likely_pathogenic	0.6166	pathogenic	-0.509	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
A/K	0.9065	likely_pathogenic	0.8898	pathogenic	-1.097	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
A/L	0.5151	ambiguous	0.4886	ambiguous	-0.509	Destabilizing	0.994	D	0.535	neutral	None	None	None	None	N
A/M	0.4463	ambiguous	0.4062	ambiguous	-0.392	Destabilizing	0.985	D	0.511	neutral	None	None	None	None	N
A/N	0.6899	likely_pathogenic	0.6533	pathogenic	-0.799	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
A/P	0.9705	likely_pathogenic	0.9593	pathogenic	-0.579	Destabilizing	1.0	D	0.861	deleterious	D	0.534831442	None	None	N
A/Q	0.7148	likely_pathogenic	0.6816	pathogenic	-1.034	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/R	0.818	likely_pathogenic	0.7979	pathogenic	-0.652	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/S	0.1154	likely_benign	0.1079	benign	-1.126	Destabilizing	0.998	D	0.499	neutral	N	0.490498059	None	None	N
A/T	0.1485	likely_benign	0.1325	benign	-1.122	Destabilizing	0.999	D	0.65	neutral	N	0.511433478	None	None	N
A/V	0.3867	ambiguous	0.3474	ambiguous	-0.579	Destabilizing	0.992	D	0.49	neutral	N	0.510940289	None	None	N
A/W	0.9449	likely_pathogenic	0.9367	pathogenic	-1.353	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/Y	0.825	likely_pathogenic	0.788	pathogenic	-0.988	Destabilizing	1.0	D	0.883	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.