TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25422	76489;76490;76491	chr2:178569868;178569867;178569866	chr2:179434595;179434594;179434593
N2AB	23781	71566;71567;71568	chr2:178569868;178569867;178569866	chr2:179434595;179434594;179434593
N2A	22854	68785;68786;68787	chr2:178569868;178569867;178569866	chr2:179434595;179434594;179434593
N2B	16357	49294;49295;49296	chr2:178569868;178569867;178569866	chr2:179434595;179434594;179434593
Novex-1	16482	49669;49670;49671	chr2:178569868;178569867;178569866	chr2:179434595;179434594;179434593
Novex-2	16549	49870;49871;49872	chr2:178569868;178569867;178569866	chr2:179434595;179434594;179434593
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: Fn3-73
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0801
• 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/L	rs751917176	0.075	0.973	N	0.597	0.267	0.437207349437	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/L	rs751917176	0.075	0.973	N	0.597	0.267	0.437207349437	gnomAD-4.0.0	2.73731E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79914E-06	2.31911E-05	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	0.305	likely_benign	0.2927	benign	-2.086	Highly Destabilizing	0.543	D	0.313	neutral	N	0.515739567	None	None	N
V/C	0.8326	likely_pathogenic	0.8164	pathogenic	-1.026	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/D	0.9931	likely_pathogenic	0.9912	pathogenic	-2.791	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
V/E	0.9847	likely_pathogenic	0.9833	pathogenic	-2.449	Highly Destabilizing	0.998	D	0.829	deleterious	N	0.513899808	None	None	N
V/F	0.675	likely_pathogenic	0.6291	pathogenic	-1.101	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/G	0.7148	likely_pathogenic	0.6721	pathogenic	-2.702	Highly Destabilizing	0.997	D	0.773	deleterious	D	0.525256114	None	None	N
V/H	0.9925	likely_pathogenic	0.9903	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/I	0.0827	likely_benign	0.084	benign	-0.272	Destabilizing	0.987	D	0.535	neutral	N	0.465905393	None	None	N
V/K	0.9877	likely_pathogenic	0.9855	pathogenic	-1.331	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/L	0.3272	likely_benign	0.3169	benign	-0.272	Destabilizing	0.973	D	0.597	neutral	N	0.457048467	None	None	N
V/M	0.3617	ambiguous	0.3515	ambiguous	-0.518	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/N	0.9688	likely_pathogenic	0.9636	pathogenic	-2.113	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/P	0.9864	likely_pathogenic	0.981	pathogenic	-0.861	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
V/Q	0.9777	likely_pathogenic	0.9746	pathogenic	-1.647	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/R	0.9756	likely_pathogenic	0.9699	pathogenic	-1.744	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
V/S	0.7767	likely_pathogenic	0.7598	pathogenic	-2.513	Highly Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
V/T	0.6105	likely_pathogenic	0.5942	pathogenic	-2.002	Highly Destabilizing	0.992	D	0.643	neutral	None	None	None	None	N
V/W	0.9952	likely_pathogenic	0.9932	pathogenic	-1.547	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/Y	0.9644	likely_pathogenic	0.9539	pathogenic	-1.281	Destabilizing	1.0	D	0.849	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.