TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16586	49981;49982;49983	chr2:178612965;178612964;178612963	chr2:179477692;179477691;179477690
N2AB	14945	45058;45059;45060	chr2:178612965;178612964;178612963	chr2:179477692;179477691;179477690
N2A	14018	42277;42278;42279	chr2:178612965;178612964;178612963	chr2:179477692;179477691;179477690
N2B	7521	22786;22787;22788	chr2:178612965;178612964;178612963	chr2:179477692;179477691;179477690
Novex-1	7646	23161;23162;23163	chr2:178612965;178612964;178612963	chr2:179477692;179477691;179477690
Novex-2	7713	23362;23363;23364	chr2:178612965;178612964;178612963	chr2:179477692;179477691;179477690
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: Fn3-8
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0976
• 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/H	rs767149437	-2.995	1.0	D	0.813	0.79	0.739165658135	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
Y/H	rs767149437	-2.995	1.0	D	0.813	0.79	0.739165658135	gnomAD-4.0.0	3.18706E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.76705E-05	0	0	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	0.9941	likely_pathogenic	0.996	pathogenic	-3.488	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/C	0.8923	likely_pathogenic	0.9121	pathogenic	-1.983	Destabilizing	1.0	D	0.875	deleterious	D	0.832415133	None	None	N
Y/D	0.9961	likely_pathogenic	0.998	pathogenic	-3.775	Highly Destabilizing	1.0	D	0.917	deleterious	D	0.831420717	None	None	N
Y/E	0.9989	likely_pathogenic	0.9994	pathogenic	-3.554	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/F	0.2582	likely_benign	0.252	benign	-1.32	Destabilizing	0.999	D	0.638	neutral	D	0.622013215	None	None	N
Y/G	0.9901	likely_pathogenic	0.9931	pathogenic	-3.904	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
Y/H	0.9719	likely_pathogenic	0.9819	pathogenic	-2.566	Highly Destabilizing	1.0	D	0.813	deleterious	D	0.832415133	None	None	N
Y/I	0.9725	likely_pathogenic	0.9801	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9995	pathogenic	-2.364	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/L	0.931	likely_pathogenic	0.9455	pathogenic	-2.079	Highly Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
Y/M	0.9782	likely_pathogenic	0.9842	pathogenic	-1.866	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/N	0.9781	likely_pathogenic	0.9857	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.831420717	None	None	N
Y/P	0.999	likely_pathogenic	0.9994	pathogenic	-2.568	Highly Destabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
Y/Q	0.9983	likely_pathogenic	0.999	pathogenic	-2.889	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/R	0.9946	likely_pathogenic	0.9968	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/S	0.9785	likely_pathogenic	0.9864	pathogenic	-3.488	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.831420717	None	None	N
Y/T	0.9919	likely_pathogenic	0.9947	pathogenic	-3.144	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
Y/V	0.9382	likely_pathogenic	0.9541	pathogenic	-2.568	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
Y/W	0.795	likely_pathogenic	0.8051	pathogenic	-0.513	Destabilizing	1.0	D	0.796	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.