TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29656	89191;89192;89193	chr2:178554145;178554144;178554143	chr2:179418872;179418871;179418870
N2AB	28015	84268;84269;84270	chr2:178554145;178554144;178554143	chr2:179418872;179418871;179418870
N2A	27088	81487;81488;81489	chr2:178554145;178554144;178554143	chr2:179418872;179418871;179418870
N2B	20591	61996;61997;61998	chr2:178554145;178554144;178554143	chr2:179418872;179418871;179418870
Novex-1	20716	62371;62372;62373	chr2:178554145;178554144;178554143	chr2:179418872;179418871;179418870
Novex-2	20783	62572;62573;62574	chr2:178554145;178554144;178554143	chr2:179418872;179418871;179418870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-104
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6791
• 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
R/G	None	None	1.0	N	0.691	0.358	0.599206028305	gnomAD-4.0.0	6.8427E-07	None	None	None	None	I	None	2.98846E-05	0	None	0	0	None	0	0	0	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
R/A	0.6513	likely_pathogenic	0.7305	pathogenic	-0.131	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
R/C	0.2675	likely_benign	0.35	ambiguous	-0.446	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
R/D	0.8741	likely_pathogenic	0.9123	pathogenic	-0.382	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
R/E	0.6	likely_pathogenic	0.6797	pathogenic	-0.264	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	I
R/F	0.7884	likely_pathogenic	0.8572	pathogenic	-0.213	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
R/G	0.5565	ambiguous	0.6721	pathogenic	-0.366	Destabilizing	1.0	D	0.691	prob.neutral	N	0.509995391	None	None	I
R/H	0.1641	likely_benign	0.2054	benign	-1.059	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
R/I	0.6052	likely_pathogenic	0.6801	pathogenic	0.474	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
R/K	0.1632	likely_benign	0.1829	benign	-0.188	Destabilizing	0.997	D	0.57	neutral	N	0.460644006	None	None	I
R/L	0.4763	ambiguous	0.5657	pathogenic	0.474	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
R/M	0.5883	likely_pathogenic	0.6747	pathogenic	-0.198	Destabilizing	1.0	D	0.771	deleterious	N	0.518404231	None	None	I
R/N	0.8235	likely_pathogenic	0.876	pathogenic	-0.249	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
R/P	0.5048	ambiguous	0.5777	pathogenic	0.292	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
R/Q	0.1783	likely_benign	0.2185	benign	-0.182	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
R/S	0.7468	likely_pathogenic	0.8236	pathogenic	-0.513	Destabilizing	1.0	D	0.739	prob.delet.	N	0.470957001	None	None	I
R/T	0.6265	likely_pathogenic	0.7133	pathogenic	-0.23	Destabilizing	1.0	D	0.735	prob.delet.	N	0.517190723	None	None	I
R/V	0.6514	likely_pathogenic	0.7167	pathogenic	0.292	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
R/W	0.3329	likely_benign	0.4327	ambiguous	-0.294	Destabilizing	1.0	D	0.789	deleterious	N	0.502982165	None	None	I
R/Y	0.5872	likely_pathogenic	0.6797	pathogenic	0.094	Stabilizing	1.0	D	0.773	deleterious	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.