TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15860	47803;47804;47805	chr2:178617507;178617506;178617505	chr2:179482234;179482233;179482232
N2AB	14219	42880;42881;42882	chr2:178617507;178617506;178617505	chr2:179482234;179482233;179482232
N2A	13292	40099;40100;40101	chr2:178617507;178617506;178617505	chr2:179482234;179482233;179482232
N2B	6795	20608;20609;20610	chr2:178617507;178617506;178617505	chr2:179482234;179482233;179482232
Novex-1	6920	20983;20984;20985	chr2:178617507;178617506;178617505	chr2:179482234;179482233;179482232
Novex-2	6987	21184;21185;21186	chr2:178617507;178617506;178617505	chr2:179482234;179482233;179482232
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-3
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.0956
• 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	rs754280245	-2.506	1.0	D	0.789	0.621	None	gnomAD-2.1.1	2.34E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.99E-05	0
P/S	rs754280245	-2.506	1.0	D	0.789	0.621	None	gnomAD-4.0.0	1.33754E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.34751E-05	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	0.7887	likely_pathogenic	0.8582	pathogenic	-1.664	Destabilizing	0.999	D	0.825	deleterious	D	0.766726748	None	None	N
P/C	0.9806	likely_pathogenic	0.9881	pathogenic	-2.118	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.9989	pathogenic	-3.375	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
P/E	0.9964	likely_pathogenic	0.9973	pathogenic	-3.297	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
P/F	0.9987	likely_pathogenic	0.9992	pathogenic	-1.158	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/G	0.9799	likely_pathogenic	0.9859	pathogenic	-1.998	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/H	0.9951	likely_pathogenic	0.9968	pathogenic	-1.428	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/I	0.9833	likely_pathogenic	0.9886	pathogenic	-0.791	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/K	0.9976	likely_pathogenic	0.9981	pathogenic	-1.617	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/L	0.949	likely_pathogenic	0.9656	pathogenic	-0.791	Destabilizing	1.0	D	0.863	deleterious	D	0.800771295	None	None	N
P/M	0.9924	likely_pathogenic	0.995	pathogenic	-1.071	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/N	0.9978	likely_pathogenic	0.9985	pathogenic	-1.958	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/Q	0.9929	likely_pathogenic	0.9954	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.800091179	None	None	N
P/R	0.9909	likely_pathogenic	0.9932	pathogenic	-1.162	Destabilizing	1.0	D	0.853	deleterious	D	0.800091179	None	None	N
P/S	0.9709	likely_pathogenic	0.9838	pathogenic	-2.297	Highly Destabilizing	1.0	D	0.789	deleterious	D	0.746121486	None	None	N
P/T	0.9672	likely_pathogenic	0.9763	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.647619774	None	None	N
P/V	0.9529	likely_pathogenic	0.9646	pathogenic	-1.056	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/W	0.9995	likely_pathogenic	0.9997	pathogenic	-1.507	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/Y	0.9988	likely_pathogenic	0.9992	pathogenic	-1.186	Destabilizing	1.0	D	0.881	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.