TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7422	22489;22490;22491	chr2:178722523;178722522;178722521	chr2:179587250;179587249;179587248
N2AB	7105	21538;21539;21540	chr2:178722523;178722522;178722521	chr2:179587250;179587249;179587248
N2A	6178	18757;18758;18759	chr2:178722523;178722522;178722521	chr2:179587250;179587249;179587248
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-59
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4561
• 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/P	None	None	0.026	N	0.189	0.276	0.293147016451	gnomAD-4.0.0	1.37003E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80056E-06	0	0
A/S	None	None	0.233	N	0.443	0.224	0.200317383148	gnomAD-4.0.0	6.85015E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00278E-07	0	0
A/T	rs2078575332	None	0.069	N	0.099	0.271	0.19670166235	gnomAD-4.0.0	1.37003E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80056E-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
A/C	0.6676	likely_pathogenic	0.5965	pathogenic	-0.721	Destabilizing	1.0	D	0.457	neutral	None	None	None	None	N
A/D	0.5246	ambiguous	0.3882	ambiguous	-0.741	Destabilizing	0.995	D	0.443	neutral	None	None	None	None	N
A/E	0.4624	ambiguous	0.3438	ambiguous	-0.855	Destabilizing	0.983	D	0.409	neutral	N	0.465543686	None	None	N
A/F	0.4229	ambiguous	0.3547	ambiguous	-0.986	Destabilizing	1.0	D	0.473	neutral	None	None	None	None	N
A/G	0.1862	likely_benign	0.1647	benign	-0.762	Destabilizing	0.797	D	0.397	neutral	N	0.493036617	None	None	N
A/H	0.6035	likely_pathogenic	0.5247	ambiguous	-0.797	Destabilizing	1.0	D	0.466	neutral	None	None	None	None	N
A/I	0.2739	likely_benign	0.2279	benign	-0.409	Destabilizing	0.997	D	0.423	neutral	None	None	None	None	N
A/K	0.686	likely_pathogenic	0.5871	pathogenic	-0.952	Destabilizing	0.995	D	0.406	neutral	None	None	None	None	N
A/L	0.211	likely_benign	0.1799	benign	-0.409	Destabilizing	0.99	D	0.396	neutral	None	None	None	None	N
A/M	0.306	likely_benign	0.2712	benign	-0.329	Destabilizing	1.0	D	0.426	neutral	None	None	None	None	N
A/N	0.3572	ambiguous	0.3036	benign	-0.552	Destabilizing	0.957	D	0.471	neutral	None	None	None	None	N
A/P	0.3445	ambiguous	0.2774	benign	-0.44	Destabilizing	0.026	N	0.189	neutral	N	0.487113824	None	None	N
A/Q	0.4506	ambiguous	0.3813	ambiguous	-0.817	Destabilizing	1.0	D	0.459	neutral	None	None	None	None	N
A/R	0.5651	likely_pathogenic	0.4733	ambiguous	-0.46	Destabilizing	0.999	D	0.451	neutral	None	None	None	None	N
A/S	0.0933	likely_benign	0.0864	benign	-0.821	Destabilizing	0.233	N	0.443	neutral	N	0.428025448	None	None	N
A/T	0.1028	likely_benign	0.0856	benign	-0.852	Destabilizing	0.069	N	0.099	neutral	N	0.379732856	None	None	N
A/V	0.1508	likely_benign	0.1213	benign	-0.44	Destabilizing	0.965	D	0.397	neutral	N	0.441725464	None	None	N
A/W	0.8151	likely_pathogenic	0.7556	pathogenic	-1.183	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
A/Y	0.5902	likely_pathogenic	0.5213	ambiguous	-0.832	Destabilizing	1.0	D	0.473	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.