TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24818	74677;74678;74679	chr2:178571680;178571679;178571678	chr2:179436407;179436406;179436405
N2AB	23177	69754;69755;69756	chr2:178571680;178571679;178571678	chr2:179436407;179436406;179436405
N2A	22250	66973;66974;66975	chr2:178571680;178571679;178571678	chr2:179436407;179436406;179436405
N2B	15753	47482;47483;47484	chr2:178571680;178571679;178571678	chr2:179436407;179436406;179436405
Novex-1	15878	47857;47858;47859	chr2:178571680;178571679;178571678	chr2:179436407;179436406;179436405
Novex-2	15945	48058;48059;48060	chr2:178571680;178571679;178571678	chr2:179436407;179436406;179436405
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-68
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.2573
• 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
M/V	None	None	None	N	0.139	0.073	0.194818534648	gnomAD-4.0.0	2.05298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79917E-06	0	1.65689E-05

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
M/A	0.4421	ambiguous	0.396	ambiguous	-1.749	Destabilizing	0.025	N	0.339	neutral	None	None	None	None	N
M/C	0.6313	likely_pathogenic	0.5986	pathogenic	-1.513	Destabilizing	0.667	D	0.495	neutral	None	None	None	None	N
M/D	0.9104	likely_pathogenic	0.8964	pathogenic	-0.467	Destabilizing	0.635	D	0.605	neutral	None	None	None	None	N
M/E	0.6824	likely_pathogenic	0.6404	pathogenic	-0.405	Destabilizing	0.364	N	0.539	neutral	None	None	None	None	N
M/F	0.2021	likely_benign	0.1898	benign	-0.632	Destabilizing	None	N	0.166	neutral	None	None	None	None	N
M/G	0.7694	likely_pathogenic	0.7319	pathogenic	-2.105	Highly Destabilizing	0.364	N	0.509	neutral	None	None	None	None	N
M/H	0.6943	likely_pathogenic	0.6569	pathogenic	-1.154	Destabilizing	0.859	D	0.527	neutral	None	None	None	None	N
M/I	0.1343	likely_benign	0.113	benign	-0.813	Destabilizing	None	N	0.139	neutral	N	0.30025806	None	None	N
M/K	0.3925	ambiguous	0.3562	ambiguous	-0.592	Destabilizing	0.301	N	0.488	neutral	N	0.407543027	None	None	N
M/L	0.1004	likely_benign	0.0956	benign	-0.813	Destabilizing	None	N	0.121	neutral	N	0.348916011	None	None	N
M/N	0.6892	likely_pathogenic	0.6432	pathogenic	-0.547	Destabilizing	0.859	D	0.615	neutral	None	None	None	None	N
M/P	0.6386	likely_pathogenic	0.6525	pathogenic	-1.098	Destabilizing	0.859	D	0.61	neutral	None	None	None	None	N
M/Q	0.4744	ambiguous	0.4411	ambiguous	-0.555	Destabilizing	0.859	D	0.516	neutral	None	None	None	None	N
M/R	0.3557	ambiguous	0.3226	benign	-0.199	Destabilizing	0.301	N	0.565	neutral	N	0.419221458	None	None	N
M/S	0.613	likely_pathogenic	0.5554	ambiguous	-1.221	Destabilizing	0.104	N	0.426	neutral	None	None	None	None	N
M/T	0.3036	likely_benign	0.2642	benign	-1.032	Destabilizing	0.081	N	0.408	neutral	N	0.413660923	None	None	N
M/V	0.0704	likely_benign	0.0647	benign	-1.098	Destabilizing	None	N	0.139	neutral	N	0.292827868	None	None	N
M/W	0.5537	ambiguous	0.537	ambiguous	-0.593	Destabilizing	0.859	D	0.494	neutral	None	None	None	None	N
M/Y	0.5199	ambiguous	0.5023	ambiguous	-0.61	Destabilizing	0.124	N	0.473	neutral	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.