TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23778	71557;71558;71559	chr2:178574800;178574799;178574798	chr2:179439527;179439526;179439525
N2AB	22137	66634;66635;66636	chr2:178574800;178574799;178574798	chr2:179439527;179439526;179439525
N2A	21210	63853;63854;63855	chr2:178574800;178574799;178574798	chr2:179439527;179439526;179439525
N2B	14713	44362;44363;44364	chr2:178574800;178574799;178574798	chr2:179439527;179439526;179439525
Novex-1	14838	44737;44738;44739	chr2:178574800;178574799;178574798	chr2:179439527;179439526;179439525
Novex-2	14905	44938;44939;44940	chr2:178574800;178574799;178574798	chr2:179439527;179439526;179439525
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: Fn3-60
• Domain position: 53
• Structural Position: 69
• Q(SASA): 0.1503
• 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
A/G	rs973981142	-1.257	1.0	N	0.619	0.381	0.499985177359	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
A/G	rs973981142	-1.257	1.0	N	0.619	0.381	0.499985177359	gnomAD-4.0.0	5.47981E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.30186E-06	0	1.65909E-05

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	0.6657	likely_pathogenic	0.711	pathogenic	-1.008	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
A/D	0.942	likely_pathogenic	0.9467	pathogenic	-1.049	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/E	0.9408	likely_pathogenic	0.9464	pathogenic	-1.024	Destabilizing	1.0	D	0.787	deleterious	N	0.493332428	None	None	N
A/F	0.8957	likely_pathogenic	0.9097	pathogenic	-0.919	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
A/G	0.3335	likely_benign	0.3469	ambiguous	-1.251	Destabilizing	1.0	D	0.619	neutral	N	0.453603391	None	None	N
A/H	0.9142	likely_pathogenic	0.9235	pathogenic	-1.394	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/I	0.8559	likely_pathogenic	0.891	pathogenic	-0.186	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/K	0.9759	likely_pathogenic	0.9793	pathogenic	-1.167	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/L	0.6331	likely_pathogenic	0.6784	pathogenic	-0.186	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
A/M	0.6904	likely_pathogenic	0.7327	pathogenic	-0.24	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/N	0.765	likely_pathogenic	0.7774	pathogenic	-1.01	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
A/P	0.975	likely_pathogenic	0.9773	pathogenic	-0.39	Destabilizing	1.0	D	0.81	deleterious	N	0.47776833	None	None	N
A/Q	0.8515	likely_pathogenic	0.8612	pathogenic	-1.066	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/R	0.9544	likely_pathogenic	0.9601	pathogenic	-0.925	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
A/S	0.1605	likely_benign	0.1671	benign	-1.456	Destabilizing	1.0	D	0.639	neutral	N	0.38951184	None	None	N
A/T	0.2803	likely_benign	0.3186	benign	-1.312	Destabilizing	1.0	D	0.763	deleterious	N	0.435590846	None	None	N
A/V	0.5708	likely_pathogenic	0.6301	pathogenic	-0.39	Destabilizing	1.0	D	0.679	prob.neutral	N	0.480115202	None	None	N
A/W	0.9841	likely_pathogenic	0.9867	pathogenic	-1.327	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
A/Y	0.9444	likely_pathogenic	0.9534	pathogenic	-0.871	Destabilizing	1.0	D	0.801	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.