TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21162	63709;63710;63711	chr2:178587923;178587922;178587921	chr2:179452650;179452649;179452648
N2AB	19521	58786;58787;58788	chr2:178587923;178587922;178587921	chr2:179452650;179452649;179452648
N2A	18594	56005;56006;56007	chr2:178587923;178587922;178587921	chr2:179452650;179452649;179452648
N2B	12097	36514;36515;36516	chr2:178587923;178587922;178587921	chr2:179452650;179452649;179452648
Novex-1	12222	36889;36890;36891	chr2:178587923;178587922;178587921	chr2:179452650;179452649;179452648
Novex-2	12289	37090;37091;37092	chr2:178587923;178587922;178587921	chr2:179452650;179452649;179452648
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-41
• Domain position: 99
• Structural Position: 126
• Q(SASA): 0.2451
• 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/P	None	None	1.0	N	0.813	0.369	0.299086750705	gnomAD-4.0.0	2.76471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.62749E-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
A/C	0.4675	ambiguous	0.4827	ambiguous	-0.871	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/D	0.4584	ambiguous	0.4441	ambiguous	-1.087	Destabilizing	1.0	D	0.798	deleterious	N	0.479761078	None	None	N
A/E	0.4169	ambiguous	0.4126	ambiguous	-1.169	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/F	0.48	ambiguous	0.4825	ambiguous	-0.981	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/G	0.138	likely_benign	0.1378	benign	-0.97	Destabilizing	0.999	D	0.722	deleterious	N	0.452249074	None	None	N
A/H	0.5795	likely_pathogenic	0.5885	pathogenic	-1.077	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
A/I	0.3444	ambiguous	0.3448	ambiguous	-0.424	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/K	0.5671	likely_pathogenic	0.5757	pathogenic	-1.229	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
A/L	0.3443	ambiguous	0.3486	ambiguous	-0.424	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/M	0.338	likely_benign	0.3496	ambiguous	-0.379	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/N	0.3328	likely_benign	0.3346	benign	-0.852	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/P	0.1244	likely_benign	0.1221	benign	-0.502	Destabilizing	1.0	D	0.813	deleterious	N	0.444146041	None	None	N
A/Q	0.468	ambiguous	0.4776	ambiguous	-1.084	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
A/R	0.527	ambiguous	0.5233	ambiguous	-0.765	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/S	0.1124	likely_benign	0.111	benign	-1.125	Destabilizing	0.999	D	0.746	deleterious	N	0.497209734	None	None	N
A/T	0.1295	likely_benign	0.1282	benign	-1.124	Destabilizing	1.0	D	0.833	deleterious	N	0.451742095	None	None	N
A/V	0.1883	likely_benign	0.185	benign	-0.502	Destabilizing	0.999	D	0.813	deleterious	N	0.494089284	None	None	N
A/W	0.7698	likely_pathogenic	0.7713	pathogenic	-1.232	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/Y	0.5793	likely_pathogenic	0.5902	pathogenic	-0.883	Destabilizing	1.0	D	0.852	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.