TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23539	70840;70841;70842	chr2:178575517;178575516;178575515	chr2:179440244;179440243;179440242
N2AB	21898	65917;65918;65919	chr2:178575517;178575516;178575515	chr2:179440244;179440243;179440242
N2A	20971	63136;63137;63138	chr2:178575517;178575516;178575515	chr2:179440244;179440243;179440242
N2B	14474	43645;43646;43647	chr2:178575517;178575516;178575515	chr2:179440244;179440243;179440242
Novex-1	14599	44020;44021;44022	chr2:178575517;178575516;178575515	chr2:179440244;179440243;179440242
Novex-2	14666	44221;44222;44223	chr2:178575517;178575516;178575515	chr2:179440244;179440243;179440242
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-59
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1748
• 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/R	None	None	1.0	N	0.876	0.68	0.846500284179	gnomAD-4.0.0	3.18286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.8659E-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
L/A	0.9515	likely_pathogenic	0.9449	pathogenic	-2.745	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
L/C	0.8904	likely_pathogenic	0.8911	pathogenic	-2.276	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9991	pathogenic	-3.254	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/E	0.9954	likely_pathogenic	0.995	pathogenic	-3.039	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.7027	likely_pathogenic	0.6889	pathogenic	-1.613	Destabilizing	1.0	D	0.834	deleterious	N	0.498362081	None	None	N
L/G	0.9917	likely_pathogenic	0.9917	pathogenic	-3.284	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/H	0.9895	likely_pathogenic	0.9893	pathogenic	-2.689	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.532483903	None	None	N
L/I	0.1775	likely_benign	0.1543	benign	-1.184	Destabilizing	0.999	D	0.661	neutral	N	0.475392533	None	None	N
L/K	0.9917	likely_pathogenic	0.9918	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/M	0.361	ambiguous	0.3504	ambiguous	-1.31	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/N	0.9941	likely_pathogenic	0.9935	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/P	0.9875	likely_pathogenic	0.9847	pathogenic	-1.687	Destabilizing	1.0	D	0.884	deleterious	N	0.458769642	None	None	N
L/Q	0.9802	likely_pathogenic	0.9796	pathogenic	-2.392	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/R	0.9822	likely_pathogenic	0.9829	pathogenic	-1.819	Destabilizing	1.0	D	0.876	deleterious	N	0.520963014	None	None	N
L/S	0.992	likely_pathogenic	0.9904	pathogenic	-3.186	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/T	0.948	likely_pathogenic	0.9322	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/V	0.174	likely_benign	0.1509	benign	-1.687	Destabilizing	0.999	D	0.661	neutral	N	0.437812793	None	None	N
L/W	0.968	likely_pathogenic	0.9675	pathogenic	-1.997	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
L/Y	0.9765	likely_pathogenic	0.9766	pathogenic	-1.757	Destabilizing	1.0	D	0.837	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.