TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25701	77326;77327;77328	chr2:178569031;178569030;178569029	chr2:179433758;179433757;179433756
N2AB	24060	72403;72404;72405	chr2:178569031;178569030;178569029	chr2:179433758;179433757;179433756
N2A	23133	69622;69623;69624	chr2:178569031;178569030;178569029	chr2:179433758;179433757;179433756
N2B	16636	50131;50132;50133	chr2:178569031;178569030;178569029	chr2:179433758;179433757;179433756
Novex-1	16761	50506;50507;50508	chr2:178569031;178569030;178569029	chr2:179433758;179433757;179433756
Novex-2	16828	50707;50708;50709	chr2:178569031;178569030;178569029	chr2:179433758;179433757;179433756
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: Fn3-75
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1549
• 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	rs374033036	-0.893	1.0	N	0.914	0.542	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	1.29299E-04	0	None	0	0	None	0	None	0	0	0
P/L	rs374033036	-0.893	1.0	N	0.914	0.542	None	gnomAD-4.0.0	3.18486E-06	None	None	None	None	N	None	1.13302E-04	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	0.097	likely_benign	0.1099	benign	-1.613	Destabilizing	1.0	D	0.827	deleterious	N	0.517302579	None	None	N
P/C	0.6088	likely_pathogenic	0.646	pathogenic	-1.227	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/D	0.9425	likely_pathogenic	0.9415	pathogenic	-2.354	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/E	0.7682	likely_pathogenic	0.7815	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/F	0.8188	likely_pathogenic	0.824	pathogenic	-1.392	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/G	0.6579	likely_pathogenic	0.6883	pathogenic	-1.902	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
P/H	0.6202	likely_pathogenic	0.6189	pathogenic	-1.396	Destabilizing	1.0	D	0.873	deleterious	D	0.522749169	None	None	N
P/I	0.4928	ambiguous	0.5037	ambiguous	-0.903	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
P/K	0.7825	likely_pathogenic	0.7931	pathogenic	-1.283	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/L	0.3459	ambiguous	0.3427	ambiguous	-0.903	Destabilizing	1.0	D	0.914	deleterious	N	0.51772274	None	None	N
P/M	0.5056	ambiguous	0.5482	ambiguous	-0.693	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.8153	likely_pathogenic	0.8154	pathogenic	-1.199	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/Q	0.4795	ambiguous	0.5068	ambiguous	-1.463	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/R	0.6647	likely_pathogenic	0.6759	pathogenic	-0.707	Destabilizing	1.0	D	0.907	deleterious	N	0.507238581	None	None	N
P/S	0.291	likely_benign	0.302	benign	-1.589	Destabilizing	1.0	D	0.859	deleterious	N	0.497590569	None	None	N
P/T	0.316	likely_benign	0.3319	benign	-1.509	Destabilizing	1.0	D	0.851	deleterious	N	0.517215761	None	None	N
P/V	0.3289	likely_benign	0.3497	ambiguous	-1.109	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/W	0.9412	likely_pathogenic	0.9452	pathogenic	-1.593	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/Y	0.8241	likely_pathogenic	0.8222	pathogenic	-1.304	Destabilizing	1.0	D	0.917	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.