TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21393	64402;64403;64404	chr2:178586724;178586723;178586722	chr2:179451451;179451450;179451449
N2AB	19752	59479;59480;59481	chr2:178586724;178586723;178586722	chr2:179451451;179451450;179451449
N2A	18825	56698;56699;56700	chr2:178586724;178586723;178586722	chr2:179451451;179451450;179451449
N2B	12328	37207;37208;37209	chr2:178586724;178586723;178586722	chr2:179451451;179451450;179451449
Novex-1	12453	37582;37583;37584	chr2:178586724;178586723;178586722	chr2:179451451;179451450;179451449
Novex-2	12520	37783;37784;37785	chr2:178586724;178586723;178586722	chr2:179451451;179451450;179451449
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-43
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2764
• Predicted PPI site: I

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
D/H	None	None	1.0	N	0.667	0.457	0.510872562601	gnomAD-4.0.0	1.59277E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43328E-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
D/A	0.9291	likely_pathogenic	0.9303	pathogenic	-0.221	Destabilizing	1.0	D	0.723	prob.delet.	N	0.471661954	None	None	I
D/C	0.9905	likely_pathogenic	0.9894	pathogenic	-0.026	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
D/E	0.9268	likely_pathogenic	0.901	pathogenic	-0.771	Destabilizing	1.0	D	0.441	neutral	N	0.482991806	None	None	I
D/F	0.9889	likely_pathogenic	0.9914	pathogenic	-0.402	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
D/G	0.8948	likely_pathogenic	0.8769	pathogenic	-0.51	Destabilizing	1.0	D	0.703	prob.neutral	N	0.499845521	None	None	I
D/H	0.9622	likely_pathogenic	0.9568	pathogenic	-0.864	Destabilizing	1.0	D	0.667	neutral	N	0.499085053	None	None	I
D/I	0.9871	likely_pathogenic	0.9874	pathogenic	0.513	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
D/K	0.9845	likely_pathogenic	0.9794	pathogenic	-0.277	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/L	0.9739	likely_pathogenic	0.9765	pathogenic	0.513	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
D/M	0.9918	likely_pathogenic	0.993	pathogenic	0.924	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/N	0.4248	ambiguous	0.381	ambiguous	-0.501	Destabilizing	1.0	D	0.709	prob.delet.	N	0.520617817	None	None	I
D/P	0.9816	likely_pathogenic	0.9802	pathogenic	0.294	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
D/Q	0.9765	likely_pathogenic	0.9737	pathogenic	-0.406	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
D/R	0.984	likely_pathogenic	0.9808	pathogenic	-0.332	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
D/S	0.7313	likely_pathogenic	0.7008	pathogenic	-0.693	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
D/T	0.8326	likely_pathogenic	0.8502	pathogenic	-0.469	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
D/V	0.9579	likely_pathogenic	0.9594	pathogenic	0.294	Stabilizing	1.0	D	0.701	prob.neutral	N	0.491830124	None	None	I
D/W	0.997	likely_pathogenic	0.9973	pathogenic	-0.454	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
D/Y	0.9238	likely_pathogenic	0.923	pathogenic	-0.226	Destabilizing	1.0	D	0.638	neutral	D	0.534079022	None	None	I

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.