TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26863	80812;80813;80814	chr2:178565545;178565544;178565543	chr2:179430272;179430271;179430270
N2AB	25222	75889;75890;75891	chr2:178565545;178565544;178565543	chr2:179430272;179430271;179430270
N2A	24295	73108;73109;73110	chr2:178565545;178565544;178565543	chr2:179430272;179430271;179430270
N2B	17798	53617;53618;53619	chr2:178565545;178565544;178565543	chr2:179430272;179430271;179430270
Novex-1	17923	53992;53993;53994	chr2:178565545;178565544;178565543	chr2:179430272;179430271;179430270
Novex-2	17990	54193;54194;54195	chr2:178565545;178565544;178565543	chr2:179430272;179430271;179430270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-83
• Domain position: 84
• Structural Position: 119
• Q(SASA): 0.7672
• 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
D/E	rs1424768327	-0.249	0.4	N	0.355	0.071	0.146414634003	gnomAD-2.1.1	6.37E-05	None	None	None	None	I	None	2.29516E-04	0	None	0	0	None	0	None	0	0	0
D/E	rs1424768327	-0.249	0.4	N	0.355	0.071	0.146414634003	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs1424768327	-0.249	0.4	N	0.355	0.071	0.146414634003	gnomAD-4.0.0	1.31515E-05	None	None	None	None	I	None	4.82625E-05	0	None	0	0	None	0	0	0	0	0
D/G	rs1340374023	-0.633	0.998	N	0.721	0.471	0.297718772494	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
D/G	rs1340374023	-0.633	0.998	N	0.721	0.471	0.297718772494	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/G	rs1340374023	-0.633	0.998	N	0.721	0.471	0.297718772494	gnomAD-4.0.0	2.56293E-06	None	None	None	None	I	None	3.38352E-05	0	None	0	0	None	0	0	0	0	0
D/N	rs776528193	-0.154	1.0	N	0.733	0.324	0.335164054921	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	1.77E-05	0
D/N	rs776528193	-0.154	1.0	N	0.733	0.324	0.335164054921	gnomAD-4.0.0	8.21162E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73732E-04	7.19657E-06	3.47907E-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
D/A	0.2448	likely_benign	0.2163	benign	-0.293	Destabilizing	0.999	D	0.705	prob.neutral	N	0.451043088	None	None	I
D/C	0.7847	likely_pathogenic	0.7697	pathogenic	0.056	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
D/E	0.1665	likely_benign	0.1593	benign	-0.434	Destabilizing	0.4	N	0.355	neutral	N	0.335429426	None	None	I
D/F	0.7011	likely_pathogenic	0.6397	pathogenic	-0.308	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
D/G	0.3971	ambiguous	0.3516	ambiguous	-0.493	Destabilizing	0.998	D	0.721	prob.delet.	N	0.481133922	None	None	I
D/H	0.4851	ambiguous	0.4469	ambiguous	-0.222	Destabilizing	1.0	D	0.689	prob.neutral	N	0.48477166	None	None	I
D/I	0.4265	ambiguous	0.3568	ambiguous	0.183	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
D/K	0.5466	ambiguous	0.4955	ambiguous	0.221	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
D/L	0.4426	ambiguous	0.3831	ambiguous	0.183	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
D/M	0.6641	likely_pathogenic	0.6133	pathogenic	0.364	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
D/N	0.1773	likely_benign	0.1547	benign	-0.007	Destabilizing	1.0	D	0.733	prob.delet.	N	0.494641937	None	None	I
D/P	0.6677	likely_pathogenic	0.6193	pathogenic	0.047	Stabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
D/Q	0.4665	ambiguous	0.4334	ambiguous	0.008	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/R	0.6379	likely_pathogenic	0.583	pathogenic	0.368	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/S	0.195	likely_benign	0.1763	benign	-0.124	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	I
D/T	0.3883	ambiguous	0.3416	ambiguous	0.025	Stabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
D/V	0.2678	likely_benign	0.2272	benign	0.047	Stabilizing	0.999	D	0.739	prob.delet.	N	0.472111794	None	None	I
D/W	0.9453	likely_pathogenic	0.9306	pathogenic	-0.201	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/Y	0.3587	ambiguous	0.3027	benign	-0.077	Destabilizing	1.0	D	0.729	prob.delet.	N	0.468330591	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.