TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8344	25255;25256;25257	chr2:178717976;178717975;178717974	chr2:179582703;179582702;179582701
N2AB	8027	24304;24305;24306	chr2:178717976;178717975;178717974	chr2:179582703;179582702;179582701
N2A	7100	21523;21524;21525	chr2:178717976;178717975;178717974	chr2:179582703;179582702;179582701
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-68
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.3413
• Predicted PPI site: I

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/E	rs748045267	-1.103	0.747	N	0.427	0.187	0.489243007833	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
A/E	rs748045267	-1.103	0.747	N	0.427	0.187	0.489243007833	gnomAD-4.0.0	1.59253E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86182E-06	0	0
A/T	rs2077751372	None	0.004	N	0.247	0.096	0.171388866994	gnomAD-4.0.0	1.36876E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79943E-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	0.4912	ambiguous	0.5139	ambiguous	-0.751	Destabilizing	0.996	D	0.484	neutral	None	None	None	None	I
A/D	0.2326	likely_benign	0.2836	benign	-1.013	Destabilizing	0.736	D	0.551	neutral	None	None	None	None	I
A/E	0.1777	likely_benign	0.2022	benign	-1.169	Destabilizing	0.747	D	0.427	neutral	N	0.404012438	None	None	I
A/F	0.2536	likely_benign	0.2713	benign	-1.138	Destabilizing	0.07	N	0.452	neutral	None	None	None	None	I
A/G	0.1508	likely_benign	0.1693	benign	-0.631	Destabilizing	0.041	N	0.344	neutral	D	0.524824063	None	None	I
A/H	0.3831	ambiguous	0.4211	ambiguous	-0.684	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	I
A/I	0.2216	likely_benign	0.2488	benign	-0.55	Destabilizing	0.948	D	0.465	neutral	None	None	None	None	I
A/K	0.3993	ambiguous	0.437	ambiguous	-0.963	Destabilizing	0.123	N	0.273	neutral	None	None	None	None	I
A/L	0.1911	likely_benign	0.2205	benign	-0.55	Destabilizing	0.839	D	0.441	neutral	None	None	None	None	I
A/M	0.1907	likely_benign	0.2022	benign	-0.435	Destabilizing	0.987	D	0.508	neutral	None	None	None	None	I
A/N	0.1978	likely_benign	0.2221	benign	-0.553	Destabilizing	0.247	N	0.535	neutral	None	None	None	None	I
A/P	0.5533	ambiguous	0.7115	pathogenic	-0.518	Destabilizing	0.937	D	0.483	neutral	N	0.493655794	None	None	I
A/Q	0.2718	likely_benign	0.2944	benign	-0.896	Destabilizing	0.973	D	0.505	neutral	None	None	None	None	I
A/R	0.3453	ambiguous	0.3852	ambiguous	-0.383	Destabilizing	0.948	D	0.456	neutral	None	None	None	None	I
A/S	0.0815	likely_benign	0.0832	benign	-0.702	Destabilizing	0.001	N	0.088	neutral	N	0.391739361	None	None	I
A/T	0.0798	likely_benign	0.0829	benign	-0.793	Destabilizing	0.004	N	0.247	neutral	N	0.403284506	None	None	I
A/V	0.1173	likely_benign	0.1294	benign	-0.518	Destabilizing	0.596	D	0.347	neutral	N	0.464218321	None	None	I
A/W	0.6486	likely_pathogenic	0.703	pathogenic	-1.272	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
A/Y	0.3765	ambiguous	0.4075	ambiguous	-0.952	Destabilizing	0.948	D	0.606	neutral	None	None	None	None	I

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.