TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16208	48847;48848;48849	chr2:178615323;178615322;178615321	chr2:179480050;179480049;179480048
N2AB	14567	43924;43925;43926	chr2:178615323;178615322;178615321	chr2:179480050;179480049;179480048
N2A	13640	41143;41144;41145	chr2:178615323;178615322;178615321	chr2:179480050;179480049;179480048
N2B	7143	21652;21653;21654	chr2:178615323;178615322;178615321	chr2:179480050;179480049;179480048
Novex-1	7268	22027;22028;22029	chr2:178615323;178615322;178615321	chr2:179480050;179480049;179480048
Novex-2	7335	22228;22229;22230	chr2:178615323;178615322;178615321	chr2:179480050;179480049;179480048
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: Fn3-5
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.5012
• 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/L	rs2057137481	None	0.012	N	0.365	0.27	0.547512163748	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs2057137481	None	0.012	N	0.365	0.27	0.547512163748	gnomAD-4.0.0	6.58423E-06	None	None	None	None	N	None	2.41639E-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
P/A	0.0683	likely_benign	0.0721	benign	-0.728	Destabilizing	0.454	N	0.397	neutral	N	0.499662396	None	None	N
P/C	0.5194	ambiguous	0.5102	ambiguous	-0.658	Destabilizing	0.998	D	0.465	neutral	None	None	None	None	N
P/D	0.5857	likely_pathogenic	0.5406	ambiguous	-0.434	Destabilizing	0.949	D	0.435	neutral	None	None	None	None	N
P/E	0.3638	ambiguous	0.3359	benign	-0.509	Destabilizing	0.842	D	0.423	neutral	None	None	None	None	N
P/F	0.5538	ambiguous	0.5168	ambiguous	-0.705	Destabilizing	0.949	D	0.474	neutral	None	None	None	None	N
P/G	0.3577	ambiguous	0.3432	ambiguous	-0.93	Destabilizing	0.728	D	0.425	neutral	None	None	None	None	N
P/H	0.3094	likely_benign	0.2808	benign	-0.45	Destabilizing	0.997	D	0.429	neutral	D	0.564549855	None	None	N
P/I	0.2485	likely_benign	0.2536	benign	-0.321	Destabilizing	0.728	D	0.437	neutral	None	None	None	None	N
P/K	0.3942	ambiguous	0.3753	ambiguous	-0.682	Destabilizing	0.842	D	0.401	neutral	None	None	None	None	N
P/L	0.1283	likely_benign	0.1218	benign	-0.321	Destabilizing	0.012	N	0.365	neutral	N	0.464813159	None	None	N
P/M	0.2456	likely_benign	0.2412	benign	-0.378	Destabilizing	0.525	D	0.367	neutral	None	None	None	None	N
P/N	0.351	ambiguous	0.3418	ambiguous	-0.389	Destabilizing	0.949	D	0.467	neutral	None	None	None	None	N
P/Q	0.2186	likely_benign	0.2056	benign	-0.597	Destabilizing	0.974	D	0.473	neutral	None	None	None	None	N
P/R	0.3027	likely_benign	0.2776	benign	-0.165	Destabilizing	0.934	D	0.48	neutral	N	0.517634538	None	None	N
P/S	0.1579	likely_benign	0.1533	benign	-0.809	Destabilizing	0.051	N	0.263	neutral	N	0.482140995	None	None	N
P/T	0.0994	likely_benign	0.0963	benign	-0.777	Destabilizing	0.051	N	0.263	neutral	N	0.486748361	None	None	N
P/V	0.1542	likely_benign	0.1567	benign	-0.42	Destabilizing	0.728	D	0.397	neutral	None	None	None	None	N
P/W	0.7591	likely_pathogenic	0.7209	pathogenic	-0.811	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	N
P/Y	0.4703	ambiguous	0.4485	ambiguous	-0.524	Destabilizing	0.991	D	0.467	neutral	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.