TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32903	98932;98933;98934	chr2:178539228;178539227;178539226	chr2:179403955;179403954;179403953
N2AB	31262	94009;94010;94011	chr2:178539228;178539227;178539226	chr2:179403955;179403954;179403953
N2A	30335	91228;91229;91230	chr2:178539228;178539227;178539226	chr2:179403955;179403954;179403953
N2B	23838	71737;71738;71739	chr2:178539228;178539227;178539226	chr2:179403955;179403954;179403953
Novex-1	23963	72112;72113;72114	chr2:178539228;178539227;178539226	chr2:179403955;179403954;179403953
Novex-2	24030	72313;72314;72315	chr2:178539228;178539227;178539226	chr2:179403955;179403954;179403953
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: Fn3-128
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.1467
• 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/S	None	None	0.79	N	0.441	0.385	0.268660756437	gnomAD-4.0.0	1.59183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.1349	likely_benign	0.1039	benign	-1.013	Destabilizing	0.984	D	0.618	neutral	N	0.513360984	None	None	N
P/C	0.7008	likely_pathogenic	0.578	pathogenic	-0.716	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/D	0.8883	likely_pathogenic	0.8233	pathogenic	-0.858	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
P/E	0.7141	likely_pathogenic	0.6118	pathogenic	-0.965	Destabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
P/F	0.7634	likely_pathogenic	0.5917	pathogenic	-1.238	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/G	0.6546	likely_pathogenic	0.5204	ambiguous	-1.184	Destabilizing	0.994	D	0.729	prob.delet.	None	None	None	None	N
P/H	0.5094	ambiguous	0.3906	ambiguous	-0.74	Destabilizing	1.0	D	0.878	deleterious	N	0.506487658	None	None	N
P/I	0.479	ambiguous	0.3487	ambiguous	-0.693	Destabilizing	0.999	D	0.908	deleterious	None	None	None	None	N
P/K	0.6452	likely_pathogenic	0.5532	ambiguous	-0.678	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
P/L	0.2656	likely_benign	0.1881	benign	-0.693	Destabilizing	0.998	D	0.837	deleterious	N	0.494624373	None	None	N
P/M	0.5665	likely_pathogenic	0.4186	ambiguous	-0.396	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/N	0.7627	likely_pathogenic	0.63	pathogenic	-0.387	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
P/Q	0.4292	ambiguous	0.3294	benign	-0.72	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
P/R	0.4977	ambiguous	0.4211	ambiguous	-0.084	Destabilizing	0.999	D	0.889	deleterious	N	0.466796428	None	None	N
P/S	0.3058	likely_benign	0.214	benign	-0.79	Destabilizing	0.79	D	0.441	neutral	N	0.464910323	None	None	N
P/T	0.2644	likely_benign	0.1885	benign	-0.803	Destabilizing	0.995	D	0.769	deleterious	N	0.467303407	None	None	N
P/V	0.3649	ambiguous	0.2669	benign	-0.765	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
P/W	0.9218	likely_pathogenic	0.8528	pathogenic	-1.281	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/Y	0.7479	likely_pathogenic	0.611	pathogenic	-0.981	Destabilizing	1.0	D	0.913	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.