TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18938	57037;57038;57039	chr2:178598898;178598897;178598896	chr2:179463625;179463624;179463623
N2AB	17297	52114;52115;52116	chr2:178598898;178598897;178598896	chr2:179463625;179463624;179463623
N2A	16370	49333;49334;49335	chr2:178598898;178598897;178598896	chr2:179463625;179463624;179463623
N2B	9873	29842;29843;29844	chr2:178598898;178598897;178598896	chr2:179463625;179463624;179463623
Novex-1	9998	30217;30218;30219	chr2:178598898;178598897;178598896	chr2:179463625;179463624;179463623
Novex-2	10065	30418;30419;30420	chr2:178598898;178598897;178598896	chr2:179463625;179463624;179463623
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: Fn3-25
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3001
• 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	1.0	N	0.835	0.43	0.352048277211	gnomAD-4.0.0	6.84429E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99659E-07	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	0.2192	likely_benign	0.235	benign	-1.393	Destabilizing	1.0	D	0.779	deleterious	N	0.519172235	None	None	N
P/C	0.8382	likely_pathogenic	0.8443	pathogenic	-0.657	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/D	0.9749	likely_pathogenic	0.9622	pathogenic	-1.219	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/E	0.8823	likely_pathogenic	0.8403	pathogenic	-1.145	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/F	0.949	likely_pathogenic	0.9449	pathogenic	-0.949	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/G	0.8854	likely_pathogenic	0.8709	pathogenic	-1.778	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/H	0.8149	likely_pathogenic	0.7767	pathogenic	-1.42	Destabilizing	1.0	D	0.835	deleterious	N	0.488854383	None	None	N
P/I	0.6939	likely_pathogenic	0.6448	pathogenic	-0.408	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/K	0.8893	likely_pathogenic	0.8547	pathogenic	-1.034	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/L	0.4985	ambiguous	0.48	ambiguous	-0.408	Destabilizing	1.0	D	0.872	deleterious	N	0.514113132	None	None	N
P/M	0.7535	likely_pathogenic	0.7219	pathogenic	-0.235	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/N	0.9208	likely_pathogenic	0.8941	pathogenic	-0.938	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/Q	0.7163	likely_pathogenic	0.6585	pathogenic	-0.986	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/R	0.7786	likely_pathogenic	0.7382	pathogenic	-0.684	Destabilizing	1.0	D	0.873	deleterious	N	0.470617862	None	None	N
P/S	0.6343	likely_pathogenic	0.6124	pathogenic	-1.496	Destabilizing	1.0	D	0.835	deleterious	N	0.473152757	None	None	N
P/T	0.4467	ambiguous	0.4228	ambiguous	-1.303	Destabilizing	1.0	D	0.837	deleterious	N	0.520905818	None	None	N
P/V	0.5081	ambiguous	0.4721	ambiguous	-0.702	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/W	0.9831	likely_pathogenic	0.9809	pathogenic	-1.292	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
P/Y	0.948	likely_pathogenic	0.9306	pathogenic	-0.913	Destabilizing	1.0	D	0.871	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.