TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30543	91852;91853;91854	chr2:178550211;178550210;178550209	chr2:179414938;179414937;179414936
N2AB	28902	86929;86930;86931	chr2:178550211;178550210;178550209	chr2:179414938;179414937;179414936
N2A	27975	84148;84149;84150	chr2:178550211;178550210;178550209	chr2:179414938;179414937;179414936
N2B	21478	64657;64658;64659	chr2:178550211;178550210;178550209	chr2:179414938;179414937;179414936
Novex-1	21603	65032;65033;65034	chr2:178550211;178550210;178550209	chr2:179414938;179414937;179414936
Novex-2	21670	65233;65234;65235	chr2:178550211;178550210;178550209	chr2:179414938;179414937;179414936
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-149
• Domain position: 12
• Structural Position: 26
• Q(SASA): 0.3582
• 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
S/R	rs1043582121	-0.17	0.901	N	0.523	0.284	0.186928172975	gnomAD-4.0.0	4.1057E-06	None	None	None	None	I	None	0	4.47247E-05	None	0	0	None	0	0	3.59825E-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
S/A	0.1067	likely_benign	0.112	benign	-0.655	Destabilizing	0.587	D	0.5	neutral	None	None	None	None	I
S/C	0.129	likely_benign	0.1308	benign	-0.406	Destabilizing	0.995	D	0.601	neutral	N	0.456278453	None	None	I
S/D	0.582	likely_pathogenic	0.5978	pathogenic	0.204	Stabilizing	0.633	D	0.471	neutral	None	None	None	None	I
S/E	0.7551	likely_pathogenic	0.7546	pathogenic	0.233	Stabilizing	0.775	D	0.458	neutral	None	None	None	None	I
S/F	0.3643	ambiguous	0.4074	ambiguous	-0.784	Destabilizing	0.987	D	0.647	neutral	None	None	None	None	I
S/G	0.1084	likely_benign	0.1147	benign	-0.929	Destabilizing	0.349	N	0.517	neutral	N	0.455264495	None	None	I
S/H	0.5013	ambiguous	0.5272	ambiguous	-1.249	Destabilizing	0.923	D	0.582	neutral	None	None	None	None	I
S/I	0.1869	likely_benign	0.2022	benign	-0.029	Destabilizing	0.949	D	0.648	neutral	N	0.473084868	None	None	I
S/K	0.868	likely_pathogenic	0.8708	pathogenic	-0.424	Destabilizing	0.633	D	0.459	neutral	None	None	None	None	I
S/L	0.1578	likely_benign	0.1715	benign	-0.029	Destabilizing	0.875	D	0.523	neutral	None	None	None	None	I
S/M	0.212	likely_benign	0.2263	benign	0.049	Stabilizing	0.996	D	0.584	neutral	None	None	None	None	I
S/N	0.117	likely_benign	0.1228	benign	-0.469	Destabilizing	0.003	N	0.189	neutral	N	0.442799246	None	None	I
S/P	0.1789	likely_benign	0.1927	benign	-0.203	Destabilizing	0.961	D	0.567	neutral	None	None	None	None	I
S/Q	0.6691	likely_pathogenic	0.6769	pathogenic	-0.502	Destabilizing	0.923	D	0.525	neutral	None	None	None	None	I
S/R	0.8499	likely_pathogenic	0.8581	pathogenic	-0.407	Destabilizing	0.901	D	0.523	neutral	N	0.462251799	None	None	I
S/T	0.0942	likely_benign	0.0977	benign	-0.503	Destabilizing	0.517	D	0.517	neutral	N	0.382961509	None	None	I
S/V	0.2118	likely_benign	0.2177	benign	-0.203	Destabilizing	0.961	D	0.566	neutral	None	None	None	None	I
S/W	0.5625	ambiguous	0.5867	pathogenic	-0.79	Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	I
S/Y	0.3053	likely_benign	0.3158	benign	-0.49	Destabilizing	0.987	D	0.648	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.