TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26625	80098;80099;80100	chr2:178566259;178566258;178566257	chr2:179430986;179430985;179430984
N2AB	24984	75175;75176;75177	chr2:178566259;178566258;178566257	chr2:179430986;179430985;179430984
N2A	24057	72394;72395;72396	chr2:178566259;178566258;178566257	chr2:179430986;179430985;179430984
N2B	17560	52903;52904;52905	chr2:178566259;178566258;178566257	chr2:179430986;179430985;179430984
Novex-1	17685	53278;53279;53280	chr2:178566259;178566258;178566257	chr2:179430986;179430985;179430984
Novex-2	17752	53479;53480;53481	chr2:178566259;178566258;178566257	chr2:179430986;179430985;179430984
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-138
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.5003
• 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
T/I	rs1705799804	None	0.002	N	0.351	0.147	0.311079019809	gnomAD-4.0.0	3.18295E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	None	0	0	0	1.43275E-05	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
T/A	0.0814	likely_benign	0.0763	benign	-0.8	Destabilizing	0.047	N	0.305	neutral	N	0.486795647	None	None	N
T/C	0.2708	likely_benign	0.2342	benign	-0.573	Destabilizing	0.983	D	0.524	neutral	None	None	None	None	N
T/D	0.4359	ambiguous	0.3581	ambiguous	-0.231	Destabilizing	0.264	N	0.509	neutral	None	None	None	None	N
T/E	0.3057	likely_benign	0.2464	benign	-0.148	Destabilizing	0.228	N	0.484	neutral	None	None	None	None	N
T/F	0.1719	likely_benign	0.1465	benign	-0.676	Destabilizing	0.716	D	0.591	neutral	None	None	None	None	N
T/G	0.238	likely_benign	0.2108	benign	-1.132	Destabilizing	0.001	N	0.351	neutral	None	None	None	None	N
T/H	0.1876	likely_benign	0.1654	benign	-1.256	Destabilizing	0.836	D	0.539	neutral	None	None	None	None	N
T/I	0.0982	likely_benign	0.0867	benign	0.017	Stabilizing	0.002	N	0.351	neutral	N	0.485696464	None	None	N
T/K	0.1798	likely_benign	0.1573	benign	-0.591	Destabilizing	0.01	N	0.277	neutral	None	None	None	None	N
T/L	0.0839	likely_benign	0.0745	benign	0.017	Stabilizing	0.049	N	0.438	neutral	None	None	None	None	N
T/M	0.0866	likely_benign	0.0794	benign	0.01	Stabilizing	0.061	N	0.378	neutral	None	None	None	None	N
T/N	0.1252	likely_benign	0.1084	benign	-0.83	Destabilizing	0.007	N	0.231	neutral	N	0.501799256	None	None	N
T/P	0.6608	likely_pathogenic	0.5811	pathogenic	-0.222	Destabilizing	0.523	D	0.589	neutral	D	0.532020285	None	None	N
T/Q	0.1955	likely_benign	0.1658	benign	-0.786	Destabilizing	0.418	N	0.579	neutral	None	None	None	None	N
T/R	0.1562	likely_benign	0.1392	benign	-0.523	Destabilizing	0.002	N	0.339	neutral	None	None	None	None	N
T/S	0.0915	likely_benign	0.0844	benign	-1.129	Destabilizing	0.003	N	0.207	neutral	N	0.472602944	None	None	N
T/V	0.0959	likely_benign	0.0877	benign	-0.222	Destabilizing	0.129	N	0.387	neutral	None	None	None	None	N
T/W	0.5079	ambiguous	0.4461	ambiguous	-0.696	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
T/Y	0.2252	likely_benign	0.1959	benign	-0.398	Destabilizing	0.836	D	0.556	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.