TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23354	70285;70286;70287	chr2:178576072;178576071;178576070	chr2:179440799;179440798;179440797
N2AB	21713	65362;65363;65364	chr2:178576072;178576071;178576070	chr2:179440799;179440798;179440797
N2A	20786	62581;62582;62583	chr2:178576072;178576071;178576070	chr2:179440799;179440798;179440797
N2B	14289	43090;43091;43092	chr2:178576072;178576071;178576070	chr2:179440799;179440798;179440797
Novex-1	14414	43465;43466;43467	chr2:178576072;178576071;178576070	chr2:179440799;179440798;179440797
Novex-2	14481	43666;43667;43668	chr2:178576072;178576071;178576070	chr2:179440799;179440798;179440797
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: Ig-129
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3468
• 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
L/P	None	None	0.994	N	0.832	0.704	0.864877026976	gnomAD-4.0.0	1.59181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85948E-06	0	0
L/R	None	None	0.976	N	0.801	0.626	0.828681824056	gnomAD-4.0.0	1.59181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85948E-06	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
L/A	0.8028	likely_pathogenic	0.7851	pathogenic	-1.924	Destabilizing	0.968	D	0.561	neutral	None	None	None	None	I
L/C	0.8791	likely_pathogenic	0.8677	pathogenic	-1.421	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
L/D	0.9933	likely_pathogenic	0.9915	pathogenic	-1.524	Destabilizing	0.991	D	0.812	deleterious	None	None	None	None	I
L/E	0.9429	likely_pathogenic	0.9308	pathogenic	-1.45	Destabilizing	0.982	D	0.748	deleterious	None	None	None	None	I
L/F	0.5627	ambiguous	0.5276	ambiguous	-1.155	Destabilizing	0.998	D	0.747	deleterious	N	0.489317315	None	None	I
L/G	0.9775	likely_pathogenic	0.9769	pathogenic	-2.326	Highly Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	I
L/H	0.795	likely_pathogenic	0.7668	pathogenic	-1.523	Destabilizing	0.998	D	0.803	deleterious	N	0.498725064	None	None	I
L/I	0.1623	likely_benign	0.1481	benign	-0.855	Destabilizing	0.979	D	0.518	neutral	N	0.45840707	None	None	I
L/K	0.8587	likely_pathogenic	0.8443	pathogenic	-1.638	Destabilizing	0.982	D	0.739	prob.delet.	None	None	None	None	I
L/M	0.2217	likely_benign	0.2066	benign	-0.778	Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	I
L/N	0.949	likely_pathogenic	0.9406	pathogenic	-1.603	Destabilizing	0.991	D	0.823	deleterious	None	None	None	None	I
L/P	0.9832	likely_pathogenic	0.982	pathogenic	-1.182	Destabilizing	0.994	D	0.832	deleterious	N	0.516829319	None	None	I
L/Q	0.765	likely_pathogenic	0.7149	pathogenic	-1.663	Destabilizing	0.682	D	0.444	neutral	None	None	None	None	I
L/R	0.7895	likely_pathogenic	0.7715	pathogenic	-1.097	Destabilizing	0.976	D	0.801	deleterious	N	0.493445145	None	None	I
L/S	0.9371	likely_pathogenic	0.9267	pathogenic	-2.253	Highly Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	I
L/T	0.7873	likely_pathogenic	0.7722	pathogenic	-2.047	Highly Destabilizing	0.991	D	0.74	deleterious	None	None	None	None	I
L/V	0.1589	likely_benign	0.15	benign	-1.182	Destabilizing	0.958	D	0.46	neutral	N	0.478104765	None	None	I
L/W	0.8233	likely_pathogenic	0.7973	pathogenic	-1.294	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
L/Y	0.8462	likely_pathogenic	0.8237	pathogenic	-1.081	Destabilizing	0.998	D	0.813	deleterious	None	None	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.