TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8240	24943;24944;24945	chr2:178718388;178718387;178718386	chr2:179583115;179583114;179583113
N2AB	7923	23992;23993;23994	chr2:178718388;178718387;178718386	chr2:179583115;179583114;179583113
N2A	6996	21211;21212;21213	chr2:178718388;178718387;178718386	chr2:179583115;179583114;179583113
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-67
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3605
• 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
Q/H	rs1350676942	None	0.882	N	0.419	0.322	0.185906805712	gnomAD-4.0.0	6.84224E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73551E-04	0	0	0
Q/R	rs747625896	-0.211	None	N	0.107	0.183	0.187945064343	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	1.44877E-04	None	0	0	None	0	None	0	0	0
Q/R	rs747625896	-0.211	None	N	0.107	0.183	0.187945064343	gnomAD-4.0.0	1.27308E-05	None	None	None	None	I	None	0	1.82907E-04	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
Q/A	0.1802	likely_benign	0.187	benign	-0.8	Destabilizing	0.098	N	0.297	neutral	None	None	None	None	I
Q/C	0.5867	likely_pathogenic	0.6452	pathogenic	-0.122	Destabilizing	0.968	D	0.506	neutral	None	None	None	None	I
Q/D	0.2931	likely_benign	0.3122	benign	-0.635	Destabilizing	0.223	N	0.351	neutral	None	None	None	None	I
Q/E	0.0764	likely_benign	0.0737	benign	-0.522	Destabilizing	None	N	0.122	neutral	N	0.444976413	None	None	I
Q/F	0.5258	ambiguous	0.567	pathogenic	-0.493	Destabilizing	0.582	D	0.582	neutral	None	None	None	None	I
Q/G	0.2384	likely_benign	0.2465	benign	-1.166	Destabilizing	0.365	N	0.361	neutral	None	None	None	None	I
Q/H	0.1493	likely_benign	0.1606	benign	-0.973	Destabilizing	0.882	D	0.419	neutral	N	0.484010943	None	None	I
Q/I	0.2697	likely_benign	0.3031	benign	0.142	Stabilizing	0.223	N	0.4	neutral	None	None	None	None	I
Q/K	0.0663	likely_benign	0.0698	benign	-0.323	Destabilizing	0.006	N	0.132	neutral	N	0.440877315	None	None	I
Q/L	0.1184	likely_benign	0.1298	benign	0.142	Stabilizing	0.001	N	0.27	neutral	N	0.49734946	None	None	I
Q/M	0.3024	likely_benign	0.3277	benign	0.608	Stabilizing	0.83	D	0.431	neutral	None	None	None	None	I
Q/N	0.2003	likely_benign	0.2212	benign	-0.918	Destabilizing	0.365	N	0.377	neutral	None	None	None	None	I
Q/P	0.1417	likely_benign	0.1493	benign	-0.141	Destabilizing	0.68	D	0.463	neutral	N	0.48265459	None	None	I
Q/R	0.0754	likely_benign	0.0825	benign	-0.272	Destabilizing	None	N	0.107	neutral	N	0.476184754	None	None	I
Q/S	0.1887	likely_benign	0.2031	benign	-1.063	Destabilizing	0.111	N	0.3	neutral	None	None	None	None	I
Q/T	0.1443	likely_benign	0.1563	benign	-0.747	Destabilizing	0.008	N	0.188	neutral	None	None	None	None	I
Q/V	0.1866	likely_benign	0.1995	benign	-0.141	Destabilizing	0.008	N	0.287	neutral	None	None	None	None	I
Q/W	0.4043	ambiguous	0.4308	ambiguous	-0.338	Destabilizing	0.991	D	0.505	neutral	None	None	None	None	I
Q/Y	0.3345	likely_benign	0.3688	ambiguous	-0.108	Destabilizing	0.896	D	0.498	neutral	None	None	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.