TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27770	83533;83534;83535	chr2:178562824;178562823;178562822	chr2:179427551;179427550;179427549
N2AB	26129	78610;78611;78612	chr2:178562824;178562823;178562822	chr2:179427551;179427550;179427549
N2A	25202	75829;75830;75831	chr2:178562824;178562823;178562822	chr2:179427551;179427550;179427549
N2B	18705	56338;56339;56340	chr2:178562824;178562823;178562822	chr2:179427551;179427550;179427549
Novex-1	18830	56713;56714;56715	chr2:178562824;178562823;178562822	chr2:179427551;179427550;179427549
Novex-2	18897	56914;56915;56916	chr2:178562824;178562823;178562822	chr2:179427551;179427550;179427549
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-90
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1406
• 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
P/A	None	None	0.98	D	0.817	0.731	0.624195876753	gnomAD-4.0.0	1.59319E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86053E-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
P/A	0.5742	likely_pathogenic	0.5671	pathogenic	-2.178	Highly Destabilizing	0.98	D	0.817	deleterious	D	0.614621539	None	None	N
P/C	0.8656	likely_pathogenic	0.8395	pathogenic	-1.96	Destabilizing	0.9	D	0.825	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.27	Highly Destabilizing	0.996	D	0.858	deleterious	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.9984	pathogenic	-3.054	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
P/F	0.9991	likely_pathogenic	0.9991	pathogenic	-1.134	Destabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
P/G	0.9847	likely_pathogenic	0.9861	pathogenic	-2.693	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/H	0.9979	likely_pathogenic	0.9979	pathogenic	-2.442	Highly Destabilizing	1.0	D	0.919	deleterious	D	0.656784424	None	None	N
P/I	0.8785	likely_pathogenic	0.8747	pathogenic	-0.725	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9993	pathogenic	-1.831	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/L	0.8817	likely_pathogenic	0.8717	pathogenic	-0.725	Destabilizing	1.0	D	0.895	deleterious	D	0.656380815	None	None	N
P/M	0.9766	likely_pathogenic	0.9754	pathogenic	-1.002	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/N	0.9977	likely_pathogenic	0.9976	pathogenic	-2.229	Highly Destabilizing	0.999	D	0.919	deleterious	None	None	None	None	N
P/Q	0.9959	likely_pathogenic	0.996	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/R	0.9969	likely_pathogenic	0.997	pathogenic	-1.655	Destabilizing	1.0	D	0.924	deleterious	D	0.65658262	None	None	N
P/S	0.9544	likely_pathogenic	0.9563	pathogenic	-2.747	Highly Destabilizing	0.999	D	0.853	deleterious	D	0.631074868	None	None	N
P/T	0.8447	likely_pathogenic	0.8548	pathogenic	-2.403	Highly Destabilizing	0.998	D	0.856	deleterious	D	0.65658262	None	None	N
P/V	0.5961	likely_pathogenic	0.6021	pathogenic	-1.186	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.724	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9996	pathogenic	-1.398	Destabilizing	1.0	D	0.945	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.