TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18416	55471;55472;55473	chr2:178602025;178602024;178602023	chr2:179466752;179466751;179466750
N2AB	16775	50548;50549;50550	chr2:178602025;178602024;178602023	chr2:179466752;179466751;179466750
N2A	15848	47767;47768;47769	chr2:178602025;178602024;178602023	chr2:179466752;179466751;179466750
N2B	9351	28276;28277;28278	chr2:178602025;178602024;178602023	chr2:179466752;179466751;179466750
Novex-1	9476	28651;28652;28653	chr2:178602025;178602024;178602023	chr2:179466752;179466751;179466750
Novex-2	9543	28852;28853;28854	chr2:178602025;178602024;178602023	chr2:179466752;179466751;179466750
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-115
• Domain position: 35
• Structural Position: 52
• Q(SASA): 0.4125
• 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
G/R	rs749556953	-0.179	1.0	N	0.786	0.514	0.559427399277	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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
G/A	0.4258	ambiguous	0.4309	ambiguous	-0.51	Destabilizing	1.0	D	0.601	neutral	N	0.483406199	None	None	N
G/C	0.5415	ambiguous	0.5716	pathogenic	-0.789	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/D	0.588	likely_pathogenic	0.6753	pathogenic	-0.357	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
G/E	0.6029	likely_pathogenic	0.7173	pathogenic	-0.447	Destabilizing	1.0	D	0.766	deleterious	N	0.517361294	None	None	N
G/F	0.9104	likely_pathogenic	0.9259	pathogenic	-0.946	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/H	0.7793	likely_pathogenic	0.8407	pathogenic	-1.004	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/I	0.8014	likely_pathogenic	0.8392	pathogenic	-0.271	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/K	0.7713	likely_pathogenic	0.8492	pathogenic	-0.872	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/L	0.844	likely_pathogenic	0.8651	pathogenic	-0.271	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/M	0.87	likely_pathogenic	0.8962	pathogenic	-0.316	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
G/N	0.5564	ambiguous	0.6468	pathogenic	-0.509	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/P	0.9631	likely_pathogenic	0.9618	pathogenic	-0.31	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/Q	0.6635	likely_pathogenic	0.7637	pathogenic	-0.684	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/R	0.6683	likely_pathogenic	0.7716	pathogenic	-0.615	Destabilizing	1.0	D	0.786	deleterious	N	0.489900659	None	None	N
G/S	0.2284	likely_benign	0.262	benign	-0.81	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
G/T	0.5293	ambiguous	0.5828	pathogenic	-0.806	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/V	0.7075	likely_pathogenic	0.755	pathogenic	-0.31	Destabilizing	1.0	D	0.767	deleterious	N	0.502524412	None	None	N
G/W	0.8012	likely_pathogenic	0.8532	pathogenic	-1.225	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
G/Y	0.8397	likely_pathogenic	0.879	pathogenic	-0.806	Destabilizing	1.0	D	0.765	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.