TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19301	58126;58127;58128	chr2:178594593;178594592;178594591	chr2:179459320;179459319;179459318
N2AB	17660	53203;53204;53205	chr2:178594593;178594592;178594591	chr2:179459320;179459319;179459318
N2A	16733	50422;50423;50424	chr2:178594593;178594592;178594591	chr2:179459320;179459319;179459318
N2B	10236	30931;30932;30933	chr2:178594593;178594592;178594591	chr2:179459320;179459319;179459318
Novex-1	10361	31306;31307;31308	chr2:178594593;178594592;178594591	chr2:179459320;179459319;179459318
Novex-2	10428	31507;31508;31509	chr2:178594593;178594592;178594591	chr2:179459320;179459319;179459318
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-28
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.06
• 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/I	rs1210344440	None	0.122	N	0.205	0.163	0.365120060079	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1210344440	None	0.122	N	0.205	0.163	0.365120060079	gnomAD-4.0.0	2.56553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79207E-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
V/A	0.6611	likely_pathogenic	0.6347	pathogenic	-2.235	Highly Destabilizing	0.91	D	0.629	neutral	N	0.511902333	None	None	N
V/C	0.9056	likely_pathogenic	0.9239	pathogenic	-2.275	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9982	pathogenic	-2.946	Highly Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/E	0.994	likely_pathogenic	0.9929	pathogenic	-2.662	Highly Destabilizing	0.998	D	0.818	deleterious	D	0.533740308	None	None	N
V/F	0.864	likely_pathogenic	0.8003	pathogenic	-1.385	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
V/G	0.937	likely_pathogenic	0.9344	pathogenic	-2.844	Highly Destabilizing	0.998	D	0.817	deleterious	N	0.515636053	None	None	N
V/H	0.9976	likely_pathogenic	0.997	pathogenic	-2.702	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/I	0.1019	likely_benign	0.0947	benign	-0.501	Destabilizing	0.122	N	0.205	neutral	N	0.448944146	None	None	N
V/K	0.995	likely_pathogenic	0.993	pathogenic	-1.928	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/L	0.5513	ambiguous	0.4658	ambiguous	-0.501	Destabilizing	0.031	N	0.307	neutral	N	0.497546169	None	None	N
V/M	0.5791	likely_pathogenic	0.5211	ambiguous	-0.887	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
V/N	0.9924	likely_pathogenic	0.9919	pathogenic	-2.487	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/P	0.9976	likely_pathogenic	0.9972	pathogenic	-1.054	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
V/Q	0.9905	likely_pathogenic	0.9887	pathogenic	-2.197	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/R	0.9903	likely_pathogenic	0.9873	pathogenic	-1.932	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/S	0.95	likely_pathogenic	0.9474	pathogenic	-3.146	Highly Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
V/T	0.8395	likely_pathogenic	0.8246	pathogenic	-2.687	Highly Destabilizing	0.985	D	0.706	prob.neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9977	pathogenic	-1.892	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
V/Y	0.9894	likely_pathogenic	0.9853	pathogenic	-1.519	Destabilizing	0.999	D	0.815	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.