TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31096	93511;93512;93513	chr2:178548340;178548339;178548338	chr2:179413067;179413066;179413065
N2AB	29455	88588;88589;88590	chr2:178548340;178548339;178548338	chr2:179413067;179413066;179413065
N2A	28528	85807;85808;85809	chr2:178548340;178548339;178548338	chr2:179413067;179413066;179413065
N2B	22031	66316;66317;66318	chr2:178548340;178548339;178548338	chr2:179413067;179413066;179413065
Novex-1	22156	66691;66692;66693	chr2:178548340;178548339;178548338	chr2:179413067;179413066;179413065
Novex-2	22223	66892;66893;66894	chr2:178548340;178548339;178548338	chr2:179413067;179413066;179413065
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-114
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.8202
• 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
Y/C	None	None	1.0	N	0.783	0.51	0.528561964389	gnomAD-4.0.0	1.08029E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.18125E-05	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
Y/A	0.8462	likely_pathogenic	0.8299	pathogenic	-0.62	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	I
Y/C	0.4007	ambiguous	0.3716	ambiguous	0.204	Stabilizing	1.0	D	0.783	deleterious	N	0.465759697	None	None	I
Y/D	0.8264	likely_pathogenic	0.7939	pathogenic	0.957	Stabilizing	1.0	D	0.748	deleterious	N	0.499927064	None	None	I
Y/E	0.9368	likely_pathogenic	0.9278	pathogenic	0.932	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
Y/F	0.0985	likely_benign	0.0918	benign	-0.349	Destabilizing	0.434	N	0.409	neutral	N	0.463492311	None	None	I
Y/G	0.8599	likely_pathogenic	0.8421	pathogenic	-0.803	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
Y/H	0.4629	ambiguous	0.4605	ambiguous	0.241	Stabilizing	1.0	D	0.655	neutral	N	0.477329812	None	None	I
Y/I	0.6831	likely_pathogenic	0.611	pathogenic	-0.168	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
Y/K	0.9425	likely_pathogenic	0.9254	pathogenic	0.329	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
Y/L	0.7075	likely_pathogenic	0.682	pathogenic	-0.168	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	I
Y/M	0.7788	likely_pathogenic	0.7258	pathogenic	None	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
Y/N	0.4166	ambiguous	0.4194	ambiguous	0.184	Stabilizing	1.0	D	0.749	deleterious	N	0.521903109	None	None	I
Y/P	0.9909	likely_pathogenic	0.9887	pathogenic	-0.299	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
Y/Q	0.8823	likely_pathogenic	0.8668	pathogenic	0.199	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
Y/R	0.8929	likely_pathogenic	0.8765	pathogenic	0.595	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
Y/S	0.7358	likely_pathogenic	0.7019	pathogenic	-0.262	Destabilizing	1.0	D	0.715	prob.delet.	N	0.472138799	None	None	I
Y/T	0.8631	likely_pathogenic	0.8255	pathogenic	-0.194	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
Y/V	0.6512	likely_pathogenic	0.5792	pathogenic	-0.299	Destabilizing	0.997	D	0.656	neutral	None	None	None	None	I
Y/W	0.6266	likely_pathogenic	0.6085	pathogenic	-0.479	Destabilizing	1.0	D	0.656	neutral	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.