TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22844	68755;68756;68757	chr2:178577896;178577895;178577894	chr2:179442623;179442622;179442621
N2AB	21203	63832;63833;63834	chr2:178577896;178577895;178577894	chr2:179442623;179442622;179442621
N2A	20276	61051;61052;61053	chr2:178577896;178577895;178577894	chr2:179442623;179442622;179442621
N2B	13779	41560;41561;41562	chr2:178577896;178577895;178577894	chr2:179442623;179442622;179442621
Novex-1	13904	41935;41936;41937	chr2:178577896;178577895;178577894	chr2:179442623;179442622;179442621
Novex-2	13971	42136;42137;42138	chr2:178577896;178577895;178577894	chr2:179442623;179442622;179442621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-54
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2192
• 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
P/T	None	None	0.999	N	0.85	0.323	0.40017627803	gnomAD-4.0.0	1.39938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.82282E-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	0.0785	likely_benign	0.0879	benign	-1.419	Destabilizing	0.767	D	0.553	neutral	N	0.496831306	None	None	N
P/C	0.5266	ambiguous	0.5491	ambiguous	-1.078	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/D	0.8289	likely_pathogenic	0.853	pathogenic	-1.497	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/E	0.4965	ambiguous	0.5242	ambiguous	-1.548	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/F	0.7277	likely_pathogenic	0.7578	pathogenic	-1.361	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/G	0.5117	ambiguous	0.5621	ambiguous	-1.671	Destabilizing	0.997	D	0.841	deleterious	None	None	None	None	N
P/H	0.4112	ambiguous	0.4184	ambiguous	-1.148	Destabilizing	1.0	D	0.895	deleterious	D	0.549576384	None	None	N
P/I	0.4397	ambiguous	0.4748	ambiguous	-0.845	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/K	0.4421	ambiguous	0.4719	ambiguous	-1.068	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/L	0.2706	likely_benign	0.2822	benign	-0.845	Destabilizing	0.999	D	0.874	deleterious	D	0.526445699	None	None	N
P/M	0.4801	ambiguous	0.5182	ambiguous	-0.607	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/N	0.649	likely_pathogenic	0.6778	pathogenic	-0.855	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/Q	0.2877	likely_benign	0.296	benign	-1.148	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/R	0.3038	likely_benign	0.3107	benign	-0.473	Destabilizing	0.999	D	0.886	deleterious	N	0.507073997	None	None	N
P/S	0.1872	likely_benign	0.2075	benign	-1.32	Destabilizing	0.998	D	0.832	deleterious	N	0.491830124	None	None	N
P/T	0.1974	likely_benign	0.2238	benign	-1.273	Destabilizing	0.999	D	0.85	deleterious	N	0.496313576	None	None	N
P/V	0.2874	likely_benign	0.3165	benign	-1.002	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
P/W	0.8908	likely_pathogenic	0.9054	pathogenic	-1.454	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/Y	0.7164	likely_pathogenic	0.742	pathogenic	-1.167	Destabilizing	1.0	D	0.912	deleterious	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.