TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6585	19978;19979;19980	chr2:178727825;178727824;178727823	chr2:179592552;179592551;179592550
N2AB	6268	19027;19028;19029	chr2:178727825;178727824;178727823	chr2:179592552;179592551;179592550
N2A	5341	16246;16247;16248	chr2:178727825;178727824;178727823	chr2:179592552;179592551;179592550
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: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-50
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2763
• 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/T	None	None	0.576	N	0.343	0.258	0.365892764245	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6525	likely_pathogenic	0.6452	pathogenic	-0.978	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
A/D	0.6286	likely_pathogenic	0.561	ambiguous	-1.308	Destabilizing	0.997	D	0.637	neutral	N	0.49752375	None	None	N
A/E	0.5741	likely_pathogenic	0.5371	ambiguous	-1.296	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
A/F	0.6123	likely_pathogenic	0.5688	pathogenic	-0.879	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
A/G	0.1991	likely_benign	0.1805	benign	-1.237	Destabilizing	0.989	D	0.518	neutral	N	0.496763281	None	None	N
A/H	0.8105	likely_pathogenic	0.7859	pathogenic	-1.432	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
A/I	0.3614	ambiguous	0.3378	benign	-0.237	Destabilizing	0.967	D	0.604	neutral	None	None	None	None	N
A/K	0.8117	likely_pathogenic	0.7972	pathogenic	-1.269	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
A/L	0.3927	ambiguous	0.3561	ambiguous	-0.237	Destabilizing	0.967	D	0.459	neutral	None	None	None	None	N
A/M	0.4171	ambiguous	0.4067	ambiguous	-0.263	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
A/N	0.5984	likely_pathogenic	0.5454	ambiguous	-1.072	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
A/P	0.8618	likely_pathogenic	0.8509	pathogenic	-0.426	Destabilizing	0.999	D	0.641	neutral	N	0.49727026	None	None	N
A/Q	0.6705	likely_pathogenic	0.6567	pathogenic	-1.166	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
A/R	0.7434	likely_pathogenic	0.7182	pathogenic	-0.997	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
A/S	0.1736	likely_benign	0.1509	benign	-1.461	Destabilizing	0.956	D	0.495	neutral	N	0.503374142	None	None	N
A/T	0.1471	likely_benign	0.1352	benign	-1.35	Destabilizing	0.576	D	0.343	neutral	N	0.504566221	None	None	N
A/V	0.1526	likely_benign	0.1431	benign	-0.426	Destabilizing	0.37	N	0.239	neutral	N	0.366435484	None	None	N
A/W	0.9248	likely_pathogenic	0.9148	pathogenic	-1.303	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	N
A/Y	0.7707	likely_pathogenic	0.7475	pathogenic	-0.869	Destabilizing	0.999	D	0.637	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.