TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20164	60715;60716;60717	chr2:178591235;178591234;178591233	chr2:179455962;179455961;179455960
N2AB	18523	55792;55793;55794	chr2:178591235;178591234;178591233	chr2:179455962;179455961;179455960
N2A	17596	53011;53012;53013	chr2:178591235;178591234;178591233	chr2:179455962;179455961;179455960
N2B	11099	33520;33521;33522	chr2:178591235;178591234;178591233	chr2:179455962;179455961;179455960
Novex-1	11224	33895;33896;33897	chr2:178591235;178591234;178591233	chr2:179455962;179455961;179455960
Novex-2	11291	34096;34097;34098	chr2:178591235;178591234;178591233	chr2:179455962;179455961;179455960
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-120
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.1449
• 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
V/E	rs794729467	-2.161	0.642	D	0.745	0.464	None	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
V/E	rs794729467	-2.161	0.642	D	0.745	0.464	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	6.56E-05	0	0	0	None	0	0	0	0	0
V/E	rs794729467	-2.161	0.642	D	0.745	0.464	None	gnomAD-4.0.0	3.7191E-06	None	None	None	None	N	None	6.67735E-05	1.66783E-05	None	0	0	None	0	0	0	0	0
V/I	rs72646843	-0.04	0.476	N	0.365	0.161	0.497871611283	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	8.27E-05	2.83E-05	None	0	5.14E-05	None	6.55E-05	None	0	7.82E-06	0
V/I	rs72646843	-0.04	0.476	N	0.365	0.161	0.497871611283	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	7.24E-05	1.96825E-04	0	0	0	None	0	0	0	2.07383E-04	0
V/I	rs72646843	-0.04	0.476	N	0.365	0.161	0.497871611283	1000 genomes	3.99361E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	1E-03	None
V/I	rs72646843	-0.04	0.476	N	0.365	0.161	0.497871611283	gnomAD-4.0.0	4.40091E-05	None	None	None	None	N	None	6.6688E-05	2.33442E-04	None	0	0	None	0	1.65289E-04	3.81506E-05	3.29562E-05	4.80292E-05
V/L	rs72646843	-0.042	0.002	N	0.13	0.188	0.511331572721	gnomAD-2.1.1	1.3082E-03	None	None	None	None	N	None	1.40152E-02	5.94732E-04	None	0	0	None	0	None	0	2.35E-05	4.22297E-04
V/L	rs72646843	-0.042	0.002	N	0.13	0.188	0.511331572721	gnomAD-3.1.2	3.75618E-03	None	None	None	None	N	None	1.29908E-02	1.50899E-03	0	0	0	None	0	0	5.88E-05	2.07383E-04	2.39464E-03
V/L	rs72646843	-0.042	0.002	N	0.13	0.188	0.511331572721	1000 genomes	4.79233E-03	None	None	None	None	N	None	1.74E-02	0	None	None	0	1E-03	None	None	None	0	None
V/L	rs72646843	-0.042	0.002	N	0.13	0.188	0.511331572721	gnomAD-4.0.0	7.14063E-04	None	None	None	None	N	None	1.35377E-02	9.0042E-04	None	0	0	None	0	9.91736E-04	2.20426E-05	3.29562E-05	7.68467E-04

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
V/A	0.3587	ambiguous	0.5588	ambiguous	-1.973	Destabilizing	0.002	N	0.138	neutral	N	0.461713947	None	None	N
V/C	0.7778	likely_pathogenic	0.8406	pathogenic	-1.609	Destabilizing	0.944	D	0.718	prob.delet.	None	None	None	None	N
V/D	0.9779	likely_pathogenic	0.9903	pathogenic	-2.655	Highly Destabilizing	0.944	D	0.806	deleterious	None	None	None	None	N
V/E	0.9533	likely_pathogenic	0.9766	pathogenic	-2.372	Highly Destabilizing	0.642	D	0.745	deleterious	D	0.524502322	None	None	N
V/F	0.4013	ambiguous	0.4914	ambiguous	-1.109	Destabilizing	0.704	D	0.746	deleterious	None	None	None	None	N
V/G	0.6363	likely_pathogenic	0.7666	pathogenic	-2.566	Highly Destabilizing	0.473	N	0.727	prob.delet.	N	0.517727519	None	None	N
V/H	0.9721	likely_pathogenic	0.9851	pathogenic	-2.341	Highly Destabilizing	0.995	D	0.744	deleterious	None	None	None	None	N
V/I	0.0895	likely_benign	0.0901	benign	-0.29	Destabilizing	0.476	N	0.365	neutral	N	0.469509498	None	None	N
V/K	0.9529	likely_pathogenic	0.9748	pathogenic	-1.794	Destabilizing	0.704	D	0.712	prob.delet.	None	None	None	None	N
V/L	0.2297	likely_benign	0.2654	benign	-0.29	Destabilizing	0.002	N	0.13	neutral	N	0.464082249	None	None	N
V/M	0.2721	likely_benign	0.3347	benign	-0.431	Destabilizing	0.085	N	0.331	neutral	None	None	None	None	N
V/N	0.9133	likely_pathogenic	0.9608	pathogenic	-2.322	Highly Destabilizing	0.944	D	0.788	deleterious	None	None	None	None	N
V/P	0.9634	likely_pathogenic	0.981	pathogenic	-0.826	Destabilizing	0.944	D	0.771	deleterious	None	None	None	None	N
V/Q	0.9228	likely_pathogenic	0.9583	pathogenic	-2.032	Highly Destabilizing	0.944	D	0.763	deleterious	None	None	None	None	N
V/R	0.9228	likely_pathogenic	0.9576	pathogenic	-1.817	Destabilizing	0.944	D	0.805	deleterious	None	None	None	None	N
V/S	0.711	likely_pathogenic	0.8614	pathogenic	-2.94	Highly Destabilizing	0.543	D	0.671	neutral	None	None	None	None	N
V/T	0.548	ambiguous	0.7123	pathogenic	-2.483	Highly Destabilizing	0.495	N	0.499	neutral	None	None	None	None	N
V/W	0.9756	likely_pathogenic	0.9847	pathogenic	-1.623	Destabilizing	0.995	D	0.736	prob.delet.	None	None	None	None	N
V/Y	0.9067	likely_pathogenic	0.9435	pathogenic	-1.209	Destabilizing	0.944	D	0.762	deleterious	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.