TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23438	70537;70538;70539	chr2:178575820;178575819;178575818	chr2:179440547;179440546;179440545
N2AB	21797	65614;65615;65616	chr2:178575820;178575819;178575818	chr2:179440547;179440546;179440545
N2A	20870	62833;62834;62835	chr2:178575820;178575819;178575818	chr2:179440547;179440546;179440545
N2B	14373	43342;43343;43344	chr2:178575820;178575819;178575818	chr2:179440547;179440546;179440545
Novex-1	14498	43717;43718;43719	chr2:178575820;178575819;178575818	chr2:179440547;179440546;179440545
Novex-2	14565	43918;43919;43920	chr2:178575820;178575819;178575818	chr2:179440547;179440546;179440545
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-58
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.24
• 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
P/L	None	None	1.0	N	0.89	0.486	0.795181792715	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
P/A	0.1151	likely_benign	0.1299	benign	-1.371	Destabilizing	0.999	D	0.845	deleterious	N	0.487403746	None	None	I
P/C	0.6624	likely_pathogenic	0.7181	pathogenic	-0.816	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
P/D	0.8524	likely_pathogenic	0.8824	pathogenic	-1.248	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
P/E	0.5614	ambiguous	0.6222	pathogenic	-1.301	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
P/F	0.8349	likely_pathogenic	0.8741	pathogenic	-1.204	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
P/G	0.5776	likely_pathogenic	0.6274	pathogenic	-1.633	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
P/H	0.4857	ambiguous	0.5492	ambiguous	-1.151	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/I	0.6549	likely_pathogenic	0.7151	pathogenic	-0.767	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
P/K	0.5258	ambiguous	0.6001	pathogenic	-1.061	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/L	0.3701	ambiguous	0.4332	ambiguous	-0.767	Destabilizing	1.0	D	0.89	deleterious	N	0.517887324	None	None	I
P/M	0.56	ambiguous	0.6246	pathogenic	-0.5	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
P/N	0.6731	likely_pathogenic	0.7181	pathogenic	-0.735	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	I
P/Q	0.3448	ambiguous	0.4099	ambiguous	-1.003	Destabilizing	1.0	D	0.85	deleterious	N	0.512492046	None	None	I
P/R	0.3854	ambiguous	0.4661	ambiguous	-0.472	Destabilizing	1.0	D	0.896	deleterious	N	0.507403165	None	None	I
P/S	0.2909	likely_benign	0.3355	benign	-1.199	Destabilizing	1.0	D	0.842	deleterious	N	0.495286391	None	None	I
P/T	0.2809	likely_benign	0.3307	benign	-1.155	Destabilizing	1.0	D	0.833	deleterious	N	0.50602404	None	None	I
P/V	0.4515	ambiguous	0.5114	ambiguous	-0.934	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	I
P/W	0.9368	likely_pathogenic	0.9544	pathogenic	-1.312	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
P/Y	0.8333	likely_pathogenic	0.8711	pathogenic	-1.055	Destabilizing	1.0	D	0.903	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.