TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31507	94744;94745;94746	chr2:178547006;178547005;178547004	chr2:179411733;179411732;179411731
N2AB	29866	89821;89822;89823	chr2:178547006;178547005;178547004	chr2:179411733;179411732;179411731
N2A	28939	87040;87041;87042	chr2:178547006;178547005;178547004	chr2:179411733;179411732;179411731
N2B	22442	67549;67550;67551	chr2:178547006;178547005;178547004	chr2:179411733;179411732;179411731
Novex-1	22567	67924;67925;67926	chr2:178547006;178547005;178547004	chr2:179411733;179411732;179411731
Novex-2	22634	68125;68126;68127	chr2:178547006;178547005;178547004	chr2:179411733;179411732;179411731
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-118
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2983
• 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	rs371097838	-1.415	0.997	N	0.456	0.357	None	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
V/A	rs371097838	-1.415	0.997	N	0.456	0.357	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs371097838	-1.415	0.997	N	0.456	0.357	None	gnomAD-4.0.0	4.35404E-06	None	None	None	None	N	None	6.69649E-05	0	None	0	0	None	1.56853E-05	0	8.50608E-07	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	0.7119	likely_pathogenic	0.669	pathogenic	-1.855	Destabilizing	0.997	D	0.456	neutral	N	0.483437831	None	None	N
V/C	0.8873	likely_pathogenic	0.8839	pathogenic	-1.548	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
V/D	0.9964	likely_pathogenic	0.9966	pathogenic	-2.431	Highly Destabilizing	0.999	D	0.741	deleterious	N	0.496315073	None	None	N
V/E	0.9889	likely_pathogenic	0.9892	pathogenic	-2.362	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
V/F	0.9053	likely_pathogenic	0.9113	pathogenic	-1.301	Destabilizing	0.999	D	0.741	deleterious	N	0.471181579	None	None	N
V/G	0.9145	likely_pathogenic	0.9132	pathogenic	-2.233	Highly Destabilizing	0.999	D	0.726	deleterious	N	0.496315073	None	None	N
V/H	0.9976	likely_pathogenic	0.9977	pathogenic	-1.759	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/I	0.1139	likely_benign	0.1202	benign	-0.866	Destabilizing	0.994	D	0.551	neutral	N	0.444744339	None	None	N
V/K	0.994	likely_pathogenic	0.9941	pathogenic	-1.476	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
V/L	0.6921	likely_pathogenic	0.7003	pathogenic	-0.866	Destabilizing	0.994	D	0.545	neutral	N	0.505427439	None	None	N
V/M	0.654	likely_pathogenic	0.6717	pathogenic	-0.851	Destabilizing	0.999	D	0.73	deleterious	None	None	None	None	N
V/N	0.9843	likely_pathogenic	0.9858	pathogenic	-1.501	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
V/P	0.912	likely_pathogenic	0.9007	pathogenic	-1.166	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
V/Q	0.9877	likely_pathogenic	0.9879	pathogenic	-1.623	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
V/R	0.9876	likely_pathogenic	0.9873	pathogenic	-1.035	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
V/S	0.9101	likely_pathogenic	0.9016	pathogenic	-2.025	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
V/T	0.7293	likely_pathogenic	0.7249	pathogenic	-1.847	Destabilizing	0.998	D	0.737	deleterious	None	None	None	None	N
V/W	0.9984	likely_pathogenic	0.9983	pathogenic	-1.601	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/Y	0.9939	likely_pathogenic	0.9937	pathogenic	-1.3	Destabilizing	0.999	D	0.754	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.