TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33402	100429;100430;100431	chr2:178536543;178536542;178536541	chr2:179401270;179401269;179401268
N2AB	31761	95506;95507;95508	chr2:178536543;178536542;178536541	chr2:179401270;179401269;179401268
N2A	30834	92725;92726;92727	chr2:178536543;178536542;178536541	chr2:179401270;179401269;179401268
N2B	24337	73234;73235;73236	chr2:178536543;178536542;178536541	chr2:179401270;179401269;179401268
Novex-1	24462	73609;73610;73611	chr2:178536543;178536542;178536541	chr2:179401270;179401269;179401268
Novex-2	24529	73810;73811;73812	chr2:178536543;178536542;178536541	chr2:179401270;179401269;179401268
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: Fn3-131
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4773
• 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/A	rs777018654	-0.255	0.001	N	0.114	0.142	0.152612264143	gnomAD-2.1.1	1.17E-05	None	None	None	None	N	None	0	1.04069E-04	None	0	0	None	0	None	0	0	0
T/A	rs777018654	-0.255	0.001	N	0.114	0.142	0.152612264143	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
T/A	rs777018654	-0.255	0.001	N	0.114	0.142	0.152612264143	gnomAD-4.0.0	4.4247E-06	None	None	None	None	N	None	0	7.14864E-05	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
T/A	0.11	likely_benign	0.1016	benign	-0.322	Destabilizing	0.001	N	0.114	neutral	N	0.496722237	None	None	N
T/C	0.4294	ambiguous	0.3711	ambiguous	-0.299	Destabilizing	0.836	D	0.589	neutral	None	None	None	None	N
T/D	0.4995	ambiguous	0.5482	ambiguous	0.225	Stabilizing	0.418	N	0.573	neutral	None	None	None	None	N
T/E	0.4378	ambiguous	0.4906	ambiguous	0.153	Stabilizing	0.418	N	0.511	neutral	None	None	None	None	N
T/F	0.2701	likely_benign	0.2689	benign	-0.806	Destabilizing	0.716	D	0.623	neutral	None	None	None	None	N
T/G	0.2718	likely_benign	0.2527	benign	-0.453	Destabilizing	0.264	N	0.524	neutral	None	None	None	None	N
T/H	0.3373	likely_benign	0.3591	ambiguous	-0.704	Destabilizing	0.983	D	0.598	neutral	None	None	None	None	N
T/I	0.2244	likely_benign	0.2064	benign	-0.098	Destabilizing	0.003	N	0.225	neutral	N	0.471863865	None	None	N
T/K	0.3599	ambiguous	0.4355	ambiguous	-0.338	Destabilizing	0.418	N	0.509	neutral	None	None	None	None	N
T/L	0.1303	likely_benign	0.1192	benign	-0.098	Destabilizing	0.001	N	0.24	neutral	None	None	None	None	N
T/M	0.1345	likely_benign	0.1204	benign	-0.01	Destabilizing	0.716	D	0.607	neutral	None	None	None	None	N
T/N	0.1607	likely_benign	0.153	benign	-0.164	Destabilizing	0.351	N	0.499	neutral	N	0.521849968	None	None	N
T/P	0.4211	ambiguous	0.411	ambiguous	-0.144	Destabilizing	0.794	D	0.632	neutral	N	0.519137737	None	None	N
T/Q	0.3387	likely_benign	0.3687	ambiguous	-0.372	Destabilizing	0.836	D	0.61	neutral	None	None	None	None	N
T/R	0.3027	likely_benign	0.389	ambiguous	-0.065	Destabilizing	0.716	D	0.632	neutral	None	None	None	None	N
T/S	0.1173	likely_benign	0.1072	benign	-0.376	Destabilizing	0.003	N	0.125	neutral	N	0.430129098	None	None	N
T/V	0.1777	likely_benign	0.1599	benign	-0.144	Destabilizing	0.129	N	0.328	neutral	None	None	None	None	N
T/W	0.6701	likely_pathogenic	0.6925	pathogenic	-0.823	Destabilizing	0.983	D	0.627	neutral	None	None	None	None	N
T/Y	0.3173	likely_benign	0.3297	benign	-0.53	Destabilizing	0.94	D	0.615	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.