TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16058	48397;48398;48399	chr2:178616619;178616618;178616617	chr2:179481346;179481345;179481344
N2AB	14417	43474;43475;43476	chr2:178616619;178616618;178616617	chr2:179481346;179481345;179481344
N2A	13490	40693;40694;40695	chr2:178616619;178616618;178616617	chr2:179481346;179481345;179481344
N2B	6993	21202;21203;21204	chr2:178616619;178616618;178616617	chr2:179481346;179481345;179481344
Novex-1	7118	21577;21578;21579	chr2:178616619;178616618;178616617	chr2:179481346;179481345;179481344
Novex-2	7185	21778;21779;21780	chr2:178616619;178616618;178616617	chr2:179481346;179481345;179481344
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-4
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1999
• 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
A/V	rs767579172	-0.625	0.977	D	0.823	0.425	0.420447328233	gnomAD-4.0.0	2.05454E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80008E-06	1.16077E-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
A/C	0.4813	ambiguous	0.545	ambiguous	-1.246	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/D	0.6158	likely_pathogenic	0.6447	pathogenic	-2.222	Highly Destabilizing	0.995	D	0.869	deleterious	None	None	None	None	N
A/E	0.3579	ambiguous	0.4057	ambiguous	-2.259	Highly Destabilizing	0.993	D	0.833	deleterious	D	0.553727164	None	None	N
A/F	0.4629	ambiguous	0.4984	ambiguous	-1.293	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
A/G	0.2147	likely_benign	0.2271	benign	-1.33	Destabilizing	0.955	D	0.75	deleterious	D	0.655165486	None	None	N
A/H	0.6148	likely_pathogenic	0.6571	pathogenic	-1.293	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/I	0.3193	likely_benign	0.3772	ambiguous	-0.65	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
A/K	0.473	ambiguous	0.5035	ambiguous	-1.279	Destabilizing	0.995	D	0.83	deleterious	None	None	None	None	N
A/L	0.2769	likely_benign	0.3177	benign	-0.65	Destabilizing	0.983	D	0.819	deleterious	None	None	None	None	N
A/M	0.3092	likely_benign	0.3395	benign	-0.572	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/N	0.4905	ambiguous	0.5318	ambiguous	-1.17	Destabilizing	0.995	D	0.876	deleterious	None	None	None	None	N
A/P	0.1627	likely_benign	0.1899	benign	-0.768	Destabilizing	0.997	D	0.839	deleterious	N	0.471905632	None	None	N
A/Q	0.384	ambiguous	0.4172	ambiguous	-1.439	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
A/R	0.4203	ambiguous	0.452	ambiguous	-0.833	Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	N
A/S	0.1143	likely_benign	0.1153	benign	-1.406	Destabilizing	0.568	D	0.493	neutral	N	0.481943742	None	None	N
A/T	0.1509	likely_benign	0.1687	benign	-1.375	Destabilizing	0.955	D	0.775	deleterious	D	0.592423311	None	None	N
A/V	0.1711	likely_benign	0.1962	benign	-0.768	Destabilizing	0.977	D	0.823	deleterious	D	0.603153603	None	None	N
A/W	0.8639	likely_pathogenic	0.8874	pathogenic	-1.577	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/Y	0.6264	likely_pathogenic	0.6633	pathogenic	-1.206	Destabilizing	1.0	D	0.881	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.