TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6012	18259;18260;18261	chr2:178730366;178730365;178730364	chr2:179595093;179595092;179595091
N2AB	5695	17308;17309;17310	chr2:178730366;178730365;178730364	chr2:179595093;179595092;179595091
N2A	4768	14527;14528;14529	chr2:178730366;178730365;178730364	chr2:179595093;179595092;179595091
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-44
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1229
• 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	None	None	1.0	D	0.896	0.743	0.812414231654	gnomAD-4.0.0	1.38655E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.75747E-04	9.07146E-07	0	0
P/S	None	None	1.0	D	0.883	0.754	0.658736925141	gnomAD-4.0.0	2.81545E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.65532E-06	0	0
P/T	None	None	1.0	D	0.882	0.75	0.695824657773	gnomAD-4.0.0	7.03863E-07	None	None	None	None	N	None	3.18634E-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	0.6997	likely_pathogenic	0.6324	pathogenic	-1.63	Destabilizing	1.0	D	0.839	deleterious	D	0.616316335	None	None	N
P/C	0.9814	likely_pathogenic	0.9696	pathogenic	-1.251	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.9983	pathogenic	-1.345	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/E	0.9961	likely_pathogenic	0.9952	pathogenic	-1.294	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/F	0.9977	likely_pathogenic	0.9966	pathogenic	-1.233	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/G	0.979	likely_pathogenic	0.9765	pathogenic	-1.993	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/H	0.9946	likely_pathogenic	0.9923	pathogenic	-1.51	Destabilizing	1.0	D	0.862	deleterious	D	0.632941109	None	None	N
P/I	0.9628	likely_pathogenic	0.9354	pathogenic	-0.706	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/K	0.9975	likely_pathogenic	0.9966	pathogenic	-1.077	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/L	0.8927	likely_pathogenic	0.8476	pathogenic	-0.706	Destabilizing	1.0	D	0.896	deleterious	D	0.632739305	None	None	N
P/M	0.9873	likely_pathogenic	0.9813	pathogenic	-0.677	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/N	0.9972	likely_pathogenic	0.9964	pathogenic	-0.978	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/Q	0.9914	likely_pathogenic	0.9885	pathogenic	-1.099	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/R	0.9898	likely_pathogenic	0.9869	pathogenic	-0.7	Destabilizing	1.0	D	0.889	deleterious	D	0.632941109	None	None	N
P/S	0.959	likely_pathogenic	0.9447	pathogenic	-1.625	Destabilizing	1.0	D	0.883	deleterious	D	0.61651814	None	None	N
P/T	0.954	likely_pathogenic	0.9293	pathogenic	-1.453	Destabilizing	1.0	D	0.882	deleterious	D	0.632739305	None	None	N
P/V	0.9151	likely_pathogenic	0.8574	pathogenic	-0.981	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/W	0.9993	likely_pathogenic	0.999	pathogenic	-1.436	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/Y	0.9984	likely_pathogenic	0.9976	pathogenic	-1.108	Destabilizing	1.0	D	0.893	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.