TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16475	49648;49649;49650	chr2:178613860;178613859;178613858	chr2:179478587;179478586;179478585
N2AB	14834	44725;44726;44727	chr2:178613860;178613859;178613858	chr2:179478587;179478586;179478585
N2A	13907	41944;41945;41946	chr2:178613860;178613859;178613858	chr2:179478587;179478586;179478585
N2B	7410	22453;22454;22455	chr2:178613860;178613859;178613858	chr2:179478587;179478586;179478585
Novex-1	7535	22828;22829;22830	chr2:178613860;178613859;178613858	chr2:179478587;179478586;179478585
Novex-2	7602	23029;23030;23031	chr2:178613860;178613859;178613858	chr2:179478587;179478586;179478585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-7
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.0763
• Predicted PPI site: I

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
D/N	rs1246365092	0.638	1.0	N	0.669	0.298	0.252162846088	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
D/N	rs1246365092	0.638	1.0	N	0.669	0.298	0.252162846088	gnomAD-4.0.0	4.79447E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.30071E-06	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
D/A	0.1664	likely_benign	0.1338	benign	-0.017	Destabilizing	1.0	D	0.725	prob.delet.	N	0.46711991	None	None	I
D/C	0.7066	likely_pathogenic	0.6328	pathogenic	0.222	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/E	0.1421	likely_benign	0.1174	benign	-0.236	Destabilizing	1.0	D	0.505	neutral	N	0.43085393	None	None	I
D/F	0.6753	likely_pathogenic	0.6035	pathogenic	-0.186	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
D/G	0.2635	likely_benign	0.2134	benign	-0.157	Destabilizing	1.0	D	0.699	prob.neutral	N	0.457123811	None	None	I
D/H	0.4338	ambiguous	0.351	ambiguous	0.08	Stabilizing	1.0	D	0.668	neutral	N	0.482506039	None	None	I
D/I	0.3442	ambiguous	0.2894	benign	0.286	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
D/K	0.3967	ambiguous	0.324	benign	0.562	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
D/L	0.3646	ambiguous	0.3046	benign	0.286	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
D/M	0.5722	likely_pathogenic	0.4861	ambiguous	0.326	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/N	0.141	likely_benign	0.1255	benign	0.411	Stabilizing	1.0	D	0.669	neutral	N	0.481028844	None	None	I
D/P	0.7457	likely_pathogenic	0.6467	pathogenic	0.206	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
D/Q	0.387	ambiguous	0.2997	benign	0.4	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
D/R	0.4851	ambiguous	0.3941	ambiguous	0.642	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
D/S	0.1568	likely_benign	0.1333	benign	0.311	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
D/T	0.2488	likely_benign	0.1993	benign	0.415	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
D/V	0.1946	likely_benign	0.1633	benign	0.206	Stabilizing	1.0	D	0.737	prob.delet.	N	0.47783414	None	None	I
D/W	0.8984	likely_pathogenic	0.8554	pathogenic	-0.154	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/Y	0.3127	likely_benign	0.2771	benign	0.04	Stabilizing	1.0	D	0.677	prob.neutral	N	0.501612672	None	None	I

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.