TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1573	4942;4943;4944	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971
N2AB	1573	4942;4943;4944	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971
N2A	1573	4942;4943;4944	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971
N2B	1527	4804;4805;4806	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971
Novex-1	1527	4804;4805;4806	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971
Novex-2	1527	4804;4805;4806	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971
Novex-3	1573	4942;4943;4944	chr2:178777246;178777245;178777244	chr2:179641973;179641972;179641971

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-7
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1302
• 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
L/V	rs2092329719	None	0.122	N	0.283	0.231	0.178374595973	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
L/V	rs2092329719	None	0.122	N	0.283	0.231	0.178374595973	gnomAD-4.0.0	3.04489E-06	None	None	None	None	N	None	1.74782E-05	0	None	0	0	None	0	0	0	0	6.8055E-05

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
L/A	0.7164	likely_pathogenic	0.6794	pathogenic	-2.503	Highly Destabilizing	0.931	D	0.687	prob.neutral	None	None	None	None	N
L/C	0.8155	likely_pathogenic	0.784	pathogenic	-1.876	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/D	0.9976	likely_pathogenic	0.9972	pathogenic	-2.272	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
L/E	0.9792	likely_pathogenic	0.9767	pathogenic	-2.117	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/F	0.4251	ambiguous	0.3831	ambiguous	-1.515	Destabilizing	0.994	D	0.725	prob.delet.	N	0.458470816	None	None	N
L/G	0.9633	likely_pathogenic	0.9555	pathogenic	-2.991	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
L/H	0.9447	likely_pathogenic	0.9357	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.837	deleterious	N	0.517155972	None	None	N
L/I	0.1325	likely_benign	0.1259	benign	-1.135	Destabilizing	0.835	D	0.545	neutral	N	0.451565784	None	None	N
L/K	0.9633	likely_pathogenic	0.9577	pathogenic	-2.082	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
L/M	0.1809	likely_benign	0.1662	benign	-1.019	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
L/N	0.9861	likely_pathogenic	0.9841	pathogenic	-2.209	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/P	0.9911	likely_pathogenic	0.9902	pathogenic	-1.567	Destabilizing	0.998	D	0.853	deleterious	D	0.543041521	None	None	N
L/Q	0.9044	likely_pathogenic	0.8908	pathogenic	-2.187	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
L/R	0.9313	likely_pathogenic	0.9229	pathogenic	-1.567	Destabilizing	0.998	D	0.817	deleterious	D	0.582431748	None	None	N
L/S	0.9529	likely_pathogenic	0.9442	pathogenic	-2.943	Highly Destabilizing	0.996	D	0.832	deleterious	None	None	None	None	N
L/T	0.7687	likely_pathogenic	0.7394	pathogenic	-2.638	Highly Destabilizing	0.97	D	0.799	deleterious	None	None	None	None	N
L/V	0.1441	likely_benign	0.1389	benign	-1.567	Destabilizing	0.122	N	0.283	neutral	N	0.386282418	None	None	N
L/W	0.8537	likely_pathogenic	0.8268	pathogenic	-1.69	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/Y	0.8979	likely_pathogenic	0.8766	pathogenic	-1.488	Destabilizing	0.999	D	0.824	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.