TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16759	50500;50501;50502	chr2:178612136;178612135;178612134	chr2:179476863;179476862;179476861
N2AB	15118	45577;45578;45579	chr2:178612136;178612135;178612134	chr2:179476863;179476862;179476861
N2A	14191	42796;42797;42798	chr2:178612136;178612135;178612134	chr2:179476863;179476862;179476861
N2B	7694	23305;23306;23307	chr2:178612136;178612135;178612134	chr2:179476863;179476862;179476861
Novex-1	7819	23680;23681;23682	chr2:178612136;178612135;178612134	chr2:179476863;179476862;179476861
Novex-2	7886	23881;23882;23883	chr2:178612136;178612135;178612134	chr2:179476863;179476862;179476861
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: Fn3-10
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3436
• 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/T	rs1374450831	-0.633	None	N	0.195	0.128	0.0716867268079	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	5.7E-05	None	0	None	0	0	0
A/T	rs1374450831	-0.633	None	N	0.195	0.128	0.0716867268079	gnomAD-4.0.0	1.37026E-06	None	None	None	None	N	None	0	0	None	0	5.08053E-05	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
A/C	0.3668	ambiguous	0.3031	benign	-0.726	Destabilizing	0.824	D	0.478	neutral	None	None	None	None	N
A/D	0.3165	likely_benign	0.2715	benign	-0.672	Destabilizing	0.149	N	0.571	neutral	None	None	None	None	N
A/E	0.2108	likely_benign	0.1999	benign	-0.717	Destabilizing	0.117	N	0.477	neutral	N	0.410240488	None	None	N
A/F	0.3862	ambiguous	0.3106	benign	-0.701	Destabilizing	0.555	D	0.611	neutral	None	None	None	None	N
A/G	0.1747	likely_benign	0.1522	benign	-0.758	Destabilizing	0.052	N	0.485	neutral	N	0.480387022	None	None	N
A/H	0.3483	ambiguous	0.315	benign	-0.874	Destabilizing	0.935	D	0.596	neutral	None	None	None	None	N
A/I	0.2265	likely_benign	0.1785	benign	-0.128	Destabilizing	0.235	N	0.537	neutral	None	None	None	None	N
A/K	0.3566	ambiguous	0.3058	benign	-1.003	Destabilizing	0.149	N	0.473	neutral	None	None	None	None	N
A/L	0.1606	likely_benign	0.1323	benign	-0.128	Destabilizing	0.081	N	0.471	neutral	None	None	None	None	N
A/M	0.1596	likely_benign	0.1382	benign	-0.243	Destabilizing	0.824	D	0.537	neutral	None	None	None	None	N
A/N	0.1794	likely_benign	0.1574	benign	-0.768	Destabilizing	0.149	N	0.596	neutral	None	None	None	None	N
A/P	0.8823	likely_pathogenic	0.7883	pathogenic	-0.226	Destabilizing	0.484	N	0.548	neutral	N	0.495361269	None	None	N
A/Q	0.224	likely_benign	0.2154	benign	-0.895	Destabilizing	0.555	D	0.542	neutral	None	None	None	None	N
A/R	0.3186	likely_benign	0.285	benign	-0.668	Destabilizing	0.38	N	0.549	neutral	None	None	None	None	N
A/S	0.0794	likely_benign	0.0771	benign	-1.07	Destabilizing	0.001	N	0.219	neutral	N	0.463693317	None	None	N
A/T	0.0561	likely_benign	0.0541	benign	-1.017	Destabilizing	None	N	0.195	neutral	N	0.369649096	None	None	N
A/V	0.1152	likely_benign	0.0992	benign	-0.226	Destabilizing	0.062	N	0.469	neutral	N	0.44968921	None	None	N
A/W	0.7564	likely_pathogenic	0.6874	pathogenic	-1.042	Destabilizing	0.935	D	0.704	prob.neutral	None	None	None	None	N
A/Y	0.5026	ambiguous	0.4181	ambiguous	-0.619	Destabilizing	0.555	D	0.611	neutral	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.