TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27676	83251;83252;83253	chr2:178563106;178563105;178563104	chr2:179427833;179427832;179427831
N2AB	26035	78328;78329;78330	chr2:178563106;178563105;178563104	chr2:179427833;179427832;179427831
N2A	25108	75547;75548;75549	chr2:178563106;178563105;178563104	chr2:179427833;179427832;179427831
N2B	18611	56056;56057;56058	chr2:178563106;178563105;178563104	chr2:179427833;179427832;179427831
Novex-1	18736	56431;56432;56433	chr2:178563106;178563105;178563104	chr2:179427833;179427832;179427831
Novex-2	18803	56632;56633;56634	chr2:178563106;178563105;178563104	chr2:179427833;179427832;179427831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-141
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4909
• 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
E/K	rs1424922146	None	0.958	N	0.563	0.439	0.374434639691	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs1424922146	None	0.958	N	0.563	0.439	0.374434639691	gnomAD-4.0.0	6.57307E-06	None	None	None	None	N	None	0	6.5548E-05	None	0	0	None	0	0	0	0	0
E/Q	rs1424922146	None	0.994	N	0.643	0.247	0.416833835346	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
E/V	rs1282696852	None	0.994	N	0.745	0.575	0.469165163779	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/V	rs1282696852	None	0.994	N	0.745	0.575	0.469165163779	gnomAD-4.0.0	6.57523E-06	None	None	None	None	N	None	0	6.55652E-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
E/A	0.4505	ambiguous	0.4116	ambiguous	-0.256	Destabilizing	0.958	D	0.644	neutral	N	0.507716923	None	None	N
E/C	0.95	likely_pathogenic	0.9454	pathogenic	-0.095	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.1974	likely_benign	0.1923	benign	-0.324	Destabilizing	0.067	N	0.241	neutral	N	0.462481951	None	None	N
E/F	0.8973	likely_pathogenic	0.8929	pathogenic	-0.102	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/G	0.6433	likely_pathogenic	0.601	pathogenic	-0.45	Destabilizing	0.988	D	0.694	prob.neutral	N	0.508477392	None	None	N
E/H	0.7994	likely_pathogenic	0.7711	pathogenic	0.191	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.5598	ambiguous	0.5305	ambiguous	0.216	Stabilizing	0.995	D	0.775	deleterious	None	None	None	None	N
E/K	0.6744	likely_pathogenic	0.6139	pathogenic	0.358	Stabilizing	0.958	D	0.563	neutral	N	0.506956455	None	None	N
E/L	0.6739	likely_pathogenic	0.6519	pathogenic	0.216	Stabilizing	0.995	D	0.768	deleterious	None	None	None	None	N
E/M	0.7123	likely_pathogenic	0.6852	pathogenic	0.185	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/N	0.5402	ambiguous	0.516	ambiguous	0.008	Stabilizing	0.982	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.9742	likely_pathogenic	0.9667	pathogenic	0.079	Stabilizing	0.995	D	0.75	deleterious	None	None	None	None	N
E/Q	0.3872	ambiguous	0.3464	ambiguous	0.055	Stabilizing	0.994	D	0.643	neutral	N	0.488763294	None	None	N
E/R	0.7797	likely_pathogenic	0.7375	pathogenic	0.581	Stabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
E/S	0.459	ambiguous	0.4324	ambiguous	-0.137	Destabilizing	0.968	D	0.605	neutral	None	None	None	None	N
E/T	0.5069	ambiguous	0.4588	ambiguous	0.025	Stabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	N
E/V	0.3836	ambiguous	0.3558	ambiguous	0.079	Stabilizing	0.994	D	0.745	deleterious	N	0.495853639	None	None	N
E/W	0.9797	likely_pathogenic	0.978	pathogenic	0.039	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.8619	likely_pathogenic	0.8481	pathogenic	0.141	Stabilizing	1.0	D	0.757	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.