TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9907	29944;29945;29946	chr2:178704753;178704752;178704751	chr2:179569480;179569479;179569478
N2AB	9590	28993;28994;28995	chr2:178704753;178704752;178704751	chr2:179569480;179569479;179569478
N2A	8663	26212;26213;26214	chr2:178704753;178704752;178704751	chr2:179569480;179569479;179569478
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-84
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4161
• 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/D	rs771151409	-0.205	0.625	None	0.381	0.071	0.386721274199	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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	0.4138	ambiguous	0.3707	ambiguous	-0.42	Destabilizing	0.454	N	0.371	neutral	None	None	None	None	N
E/C	0.9758	likely_pathogenic	0.9754	pathogenic	-0.25	Destabilizing	0.998	D	0.382	neutral	None	None	None	None	N
E/D	0.4436	ambiguous	0.4211	ambiguous	-0.399	Destabilizing	0.625	D	0.381	neutral	None	None	None	None	N
E/F	0.972	likely_pathogenic	0.963	pathogenic	-0.155	Destabilizing	0.991	D	0.401	neutral	None	None	None	None	N
E/G	0.4237	ambiguous	0.3636	ambiguous	-0.653	Destabilizing	0.801	D	0.402	neutral	None	None	None	None	N
E/H	0.8459	likely_pathogenic	0.8275	pathogenic	0.05	Stabilizing	0.974	D	0.387	neutral	None	None	None	None	N
E/I	0.8112	likely_pathogenic	0.7786	pathogenic	0.173	Stabilizing	0.949	D	0.405	neutral	None	None	None	None	N
E/K	0.322	likely_benign	0.2739	benign	-0.013	Destabilizing	0.454	N	0.392	neutral	None	None	None	None	N
E/L	0.8324	likely_pathogenic	0.8103	pathogenic	0.173	Stabilizing	0.842	D	0.391	neutral	None	None	None	None	N
E/M	0.8578	likely_pathogenic	0.8328	pathogenic	0.182	Stabilizing	0.991	D	0.387	neutral	None	None	None	None	N
E/N	0.6625	likely_pathogenic	0.6247	pathogenic	-0.274	Destabilizing	0.842	D	0.337	neutral	None	None	None	None	N
E/P	0.9569	likely_pathogenic	0.9422	pathogenic	-0.004	Destabilizing	0.974	D	0.397	neutral	None	None	None	None	N
E/Q	0.2637	likely_benign	0.2477	benign	-0.21	Destabilizing	0.051	N	0.193	neutral	None	None	None	None	N
E/R	0.5304	ambiguous	0.4664	ambiguous	0.306	Stabilizing	0.728	D	0.379	neutral	None	None	None	None	N
E/S	0.4756	ambiguous	0.4311	ambiguous	-0.489	Destabilizing	0.08	N	0.102	neutral	None	None	None	None	N
E/T	0.5117	ambiguous	0.4584	ambiguous	-0.303	Destabilizing	0.067	N	0.174	neutral	None	None	None	None	N
E/V	0.6069	likely_pathogenic	0.5654	pathogenic	-0.004	Destabilizing	0.801	D	0.397	neutral	None	None	None	None	N
E/W	0.9899	likely_pathogenic	0.9871	pathogenic	0.016	Stabilizing	0.998	D	0.423	neutral	None	None	None	None	N
E/Y	0.9462	likely_pathogenic	0.9361	pathogenic	0.08	Stabilizing	0.991	D	0.405	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.