TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17036	51331;51332;51333	chr2:178611023;178611022;178611021	chr2:179475750;179475749;179475748
N2AB	15395	46408;46409;46410	chr2:178611023;178611022;178611021	chr2:179475750;179475749;179475748
N2A	14468	43627;43628;43629	chr2:178611023;178611022;178611021	chr2:179475750;179475749;179475748
N2B	7971	24136;24137;24138	chr2:178611023;178611022;178611021	chr2:179475750;179475749;179475748
Novex-1	8096	24511;24512;24513	chr2:178611023;178611022;178611021	chr2:179475750;179475749;179475748
Novex-2	8163	24712;24713;24714	chr2:178611023;178611022;178611021	chr2:179475750;179475749;179475748
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-111
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.204
• 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
A/P	rs541142672	None	0.773	D	0.519	0.505	0.530011692926	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/P	rs541142672	None	0.773	D	0.519	0.505	0.530011692926	gnomAD-4.0.0	2.56628E-06	None	None	None	None	I	None	1.69428E-05	0	None	0	0	None	0	0	2.39709E-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
A/C	0.4797	ambiguous	0.464	ambiguous	-0.953	Destabilizing	0.981	D	0.496	neutral	None	None	None	None	I
A/D	0.361	ambiguous	0.345	ambiguous	-0.837	Destabilizing	0.69	D	0.553	neutral	None	None	None	None	I
A/E	0.3203	likely_benign	0.3004	benign	-0.906	Destabilizing	0.193	N	0.473	neutral	N	0.512643924	None	None	I
A/F	0.5053	ambiguous	0.4753	ambiguous	-1.024	Destabilizing	0.818	D	0.575	neutral	None	None	None	None	I
A/G	0.2141	likely_benign	0.2165	benign	-1.01	Destabilizing	0.324	N	0.441	neutral	D	0.557207364	None	None	I
A/H	0.5535	ambiguous	0.5523	ambiguous	-1.101	Destabilizing	0.944	D	0.533	neutral	None	None	None	None	I
A/I	0.2683	likely_benign	0.2433	benign	-0.408	Destabilizing	0.241	N	0.489	neutral	None	None	None	None	I
A/K	0.508	ambiguous	0.4877	ambiguous	-1.077	Destabilizing	0.002	N	0.318	neutral	None	None	None	None	I
A/L	0.2654	likely_benign	0.2491	benign	-0.408	Destabilizing	0.116	N	0.471	neutral	None	None	None	None	I
A/M	0.2734	likely_benign	0.2492	benign	-0.394	Destabilizing	0.818	D	0.503	neutral	None	None	None	None	I
A/N	0.3486	ambiguous	0.3341	benign	-0.778	Destabilizing	0.69	D	0.559	neutral	None	None	None	None	I
A/P	0.938	likely_pathogenic	0.935	pathogenic	-0.499	Destabilizing	0.773	D	0.519	neutral	D	0.623088609	None	None	I
A/Q	0.3895	ambiguous	0.3807	ambiguous	-0.978	Destabilizing	0.527	D	0.527	neutral	None	None	None	None	I
A/R	0.4949	ambiguous	0.4663	ambiguous	-0.701	Destabilizing	0.527	D	0.511	neutral	None	None	None	None	I
A/S	0.1034	likely_benign	0.1039	benign	-1.127	Destabilizing	0.09	N	0.455	neutral	N	0.514737144	None	None	I
A/T	0.0775	likely_benign	0.0726	benign	-1.101	Destabilizing	0.003	N	0.123	neutral	N	0.504478537	None	None	I
A/V	0.1311	likely_benign	0.1192	benign	-0.499	Destabilizing	0.006	N	0.361	neutral	N	0.481752431	None	None	I
A/W	0.8893	likely_pathogenic	0.8774	pathogenic	-1.275	Destabilizing	0.981	D	0.638	neutral	None	None	None	None	I
A/Y	0.6335	likely_pathogenic	0.618	pathogenic	-0.893	Destabilizing	0.932	D	0.569	neutral	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.