TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25922	77989;77990;77991	chr2:178568368;178568367;178568366	chr2:179433095;179433094;179433093
N2AB	24281	73066;73067;73068	chr2:178568368;178568367;178568366	chr2:179433095;179433094;179433093
N2A	23354	70285;70286;70287	chr2:178568368;178568367;178568366	chr2:179433095;179433094;179433093
N2B	16857	50794;50795;50796	chr2:178568368;178568367;178568366	chr2:179433095;179433094;179433093
Novex-1	16982	51169;51170;51171	chr2:178568368;178568367;178568366	chr2:179433095;179433094;179433093
Novex-2	17049	51370;51371;51372	chr2:178568368;178568367;178568366	chr2:179433095;179433094;179433093
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-76
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.7359
• 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/R	None	None	0.684	N	0.514	0.211	0.168933306366	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	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	0.1835	likely_benign	0.1777	benign	-0.069	Destabilizing	0.543	D	0.519	neutral	None	None	None	None	I
Q/C	0.7661	likely_pathogenic	0.7786	pathogenic	0.073	Stabilizing	0.996	D	0.56	neutral	None	None	None	None	I
Q/D	0.5009	ambiguous	0.5399	ambiguous	-0.046	Destabilizing	0.59	D	0.449	neutral	None	None	None	None	I
Q/E	0.1391	likely_benign	0.1656	benign	-0.095	Destabilizing	0.007	N	0.167	neutral	N	0.39651517	None	None	I
Q/F	0.7893	likely_pathogenic	0.8154	pathogenic	-0.424	Destabilizing	0.984	D	0.533	neutral	None	None	None	None	I
Q/G	0.3657	ambiguous	0.3927	ambiguous	-0.199	Destabilizing	0.742	D	0.561	neutral	None	None	None	None	I
Q/H	0.2526	likely_benign	0.2895	benign	-0.004	Destabilizing	0.939	D	0.449	neutral	N	0.467000692	None	None	I
Q/I	0.4356	ambiguous	0.4726	ambiguous	0.175	Stabilizing	0.953	D	0.552	neutral	None	None	None	None	I
Q/K	0.2019	likely_benign	0.2594	benign	0.079	Stabilizing	0.309	N	0.484	neutral	N	0.465953826	None	None	I
Q/L	0.183	likely_benign	0.1959	benign	0.175	Stabilizing	0.684	D	0.551	neutral	N	0.512843696	None	None	I
Q/M	0.3883	ambiguous	0.3983	ambiguous	0.207	Stabilizing	0.984	D	0.439	neutral	None	None	None	None	I
Q/N	0.2727	likely_benign	0.2911	benign	-0.119	Destabilizing	0.742	D	0.455	neutral	None	None	None	None	I
Q/P	0.0873	likely_benign	0.084	benign	0.119	Stabilizing	0.003	N	0.162	neutral	N	0.387106253	None	None	I
Q/R	0.221	likely_benign	0.2595	benign	0.28	Stabilizing	0.684	D	0.514	neutral	N	0.488350683	None	None	I
Q/S	0.2023	likely_benign	0.1961	benign	-0.123	Destabilizing	0.742	D	0.454	neutral	None	None	None	None	I
Q/T	0.1999	likely_benign	0.2124	benign	-0.042	Destabilizing	0.742	D	0.544	neutral	None	None	None	None	I
Q/V	0.268	likely_benign	0.2762	benign	0.119	Stabilizing	0.854	D	0.523	neutral	None	None	None	None	I
Q/W	0.7749	likely_pathogenic	0.8081	pathogenic	-0.482	Destabilizing	0.996	D	0.635	neutral	None	None	None	None	I
Q/Y	0.6038	likely_pathogenic	0.6601	pathogenic	-0.192	Destabilizing	0.984	D	0.5	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.