TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32617	98074;98075;98076	chr2:178540317;178540316;178540315	chr2:179405044;179405043;179405042
N2AB	30976	93151;93152;93153	chr2:178540317;178540316;178540315	chr2:179405044;179405043;179405042
N2A	30049	90370;90371;90372	chr2:178540317;178540316;178540315	chr2:179405044;179405043;179405042
N2B	23552	70879;70880;70881	chr2:178540317;178540316;178540315	chr2:179405044;179405043;179405042
Novex-1	23677	71254;71255;71256	chr2:178540317;178540316;178540315	chr2:179405044;179405043;179405042
Novex-2	23744	71455;71456;71457	chr2:178540317;178540316;178540315	chr2:179405044;179405043;179405042
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-126
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0926
• 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
V/A	rs398124461	-2.61	0.939	N	0.617	0.283	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	1.56E-05	0
V/A	rs398124461	-2.61	0.939	N	0.617	0.283	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/A	rs398124461	-2.61	0.939	N	0.617	0.283	None	gnomAD-4.0.0	1.11555E-05	None	None	None	None	N	None	0	1.66722E-05	None	0	0	None	0	0	1.44103E-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
V/A	0.6795	likely_pathogenic	0.6442	pathogenic	-2.284	Highly Destabilizing	0.939	D	0.617	neutral	N	0.491065701	None	None	N
V/C	0.916	likely_pathogenic	0.9051	pathogenic	-2.65	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/D	0.9983	likely_pathogenic	0.9982	pathogenic	-2.695	Highly Destabilizing	0.997	D	0.875	deleterious	D	0.542463267	None	None	N
V/E	0.9949	likely_pathogenic	0.9946	pathogenic	-2.42	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
V/F	0.8597	likely_pathogenic	0.8308	pathogenic	-1.48	Destabilizing	0.982	D	0.849	deleterious	N	0.50207402	None	None	N
V/G	0.9341	likely_pathogenic	0.9269	pathogenic	-2.86	Highly Destabilizing	0.997	D	0.873	deleterious	D	0.530093003	None	None	N
V/H	0.9979	likely_pathogenic	0.9976	pathogenic	-2.602	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
V/I	0.1008	likely_benign	0.0994	benign	-0.633	Destabilizing	0.046	N	0.201	neutral	N	0.486081169	None	None	N
V/K	0.9957	likely_pathogenic	0.9954	pathogenic	-1.802	Destabilizing	0.993	D	0.873	deleterious	None	None	None	None	N
V/L	0.6271	likely_pathogenic	0.5839	pathogenic	-0.633	Destabilizing	0.76	D	0.487	neutral	N	0.515763784	None	None	N
V/M	0.7146	likely_pathogenic	0.6612	pathogenic	-1.237	Destabilizing	0.986	D	0.751	deleterious	None	None	None	None	N
V/N	0.9922	likely_pathogenic	0.9912	pathogenic	-2.319	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
V/P	0.9972	likely_pathogenic	0.9974	pathogenic	-1.162	Destabilizing	0.998	D	0.878	deleterious	None	None	None	None	N
V/Q	0.9923	likely_pathogenic	0.9917	pathogenic	-2.057	Highly Destabilizing	0.998	D	0.886	deleterious	None	None	None	None	N
V/R	0.9895	likely_pathogenic	0.9893	pathogenic	-1.828	Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
V/S	0.9531	likely_pathogenic	0.9429	pathogenic	-3.041	Highly Destabilizing	0.993	D	0.869	deleterious	None	None	None	None	N
V/T	0.8803	likely_pathogenic	0.8528	pathogenic	-2.591	Highly Destabilizing	0.953	D	0.707	prob.neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9983	pathogenic	-1.817	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9888	likely_pathogenic	0.9871	pathogenic	-1.521	Destabilizing	0.998	D	0.848	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.