TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8713	26362;26363;26364	chr2:178715049;178715048;178715047	chr2:179579776;179579775;179579774
N2AB	8396	25411;25412;25413	chr2:178715049;178715048;178715047	chr2:179579776;179579775;179579774
N2A	7469	22630;22631;22632	chr2:178715049;178715048;178715047	chr2:179579776;179579775;179579774
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-72
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1193
• 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
Y/C	rs1294600680	-1.703	1.0	D	0.873	0.845	0.880723162625	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/C	rs1294600680	-1.703	1.0	D	0.873	0.845	0.880723162625	gnomAD-4.0.0	1.59176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85917E-06	0	0
Y/D	None	None	1.0	D	0.874	0.828	0.914177712444	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9966	likely_pathogenic	0.9981	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/C	0.9633	likely_pathogenic	0.9814	pathogenic	-1.701	Destabilizing	1.0	D	0.873	deleterious	D	0.659924006	None	None	N
Y/D	0.9983	likely_pathogenic	0.9991	pathogenic	-2.739	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.659924006	None	None	N
Y/E	0.999	likely_pathogenic	0.9994	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/F	0.2118	likely_benign	0.2296	benign	-0.711	Destabilizing	1.0	D	0.68	prob.neutral	D	0.606627936	None	None	N
Y/G	0.9932	likely_pathogenic	0.9961	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/H	0.9835	likely_pathogenic	0.9902	pathogenic	-1.906	Destabilizing	1.0	D	0.785	deleterious	D	0.643470676	None	None	N
Y/I	0.8414	likely_pathogenic	0.8721	pathogenic	-0.686	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9993	pathogenic	-1.987	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/L	0.845	likely_pathogenic	0.8617	pathogenic	-0.686	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/M	0.9598	likely_pathogenic	0.9704	pathogenic	-0.795	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9854	likely_pathogenic	0.9916	pathogenic	-2.911	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.659924006	None	None	N
Y/P	0.9991	likely_pathogenic	0.9994	pathogenic	-1.192	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/Q	0.9987	likely_pathogenic	0.9993	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/R	0.9969	likely_pathogenic	0.998	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9933	likely_pathogenic	0.9963	pathogenic	-3.242	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.659924006	None	None	N
Y/T	0.9952	likely_pathogenic	0.9972	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/V	0.8615	likely_pathogenic	0.8886	pathogenic	-1.192	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.8553	likely_pathogenic	0.8863	pathogenic	-0.11	Destabilizing	1.0	D	0.78	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.