TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23041	69346;69347;69348	chr2:178577214;178577213;178577212	chr2:179441941;179441940;179441939
N2AB	21400	64423;64424;64425	chr2:178577214;178577213;178577212	chr2:179441941;179441940;179441939
N2A	20473	61642;61643;61644	chr2:178577214;178577213;178577212	chr2:179441941;179441940;179441939
N2B	13976	42151;42152;42153	chr2:178577214;178577213;178577212	chr2:179441941;179441940;179441939
Novex-1	14101	42526;42527;42528	chr2:178577214;178577213;178577212	chr2:179441941;179441940;179441939
Novex-2	14168	42727;42728;42729	chr2:178577214;178577213;178577212	chr2:179441941;179441940;179441939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-55
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1092
• 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
P/R	rs1174533300	None	1.0	D	0.831	0.526	0.573099714865	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.9292	likely_pathogenic	0.9115	pathogenic	-1.774	Destabilizing	0.999	D	0.823	deleterious	D	0.52822599	None	None	N
P/C	0.9941	likely_pathogenic	0.9929	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.214	Highly Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/E	0.9991	likely_pathogenic	0.9992	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9997	pathogenic	-1.198	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/G	0.9974	likely_pathogenic	0.9975	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/H	0.9991	likely_pathogenic	0.9991	pathogenic	-1.507	Destabilizing	1.0	D	0.769	deleterious	D	0.555991484	None	None	N
P/I	0.9953	likely_pathogenic	0.9922	pathogenic	-0.86	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/K	0.9995	likely_pathogenic	0.9996	pathogenic	-1.586	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/L	0.9825	likely_pathogenic	0.9779	pathogenic	-0.86	Destabilizing	1.0	D	0.833	deleterious	D	0.544470594	None	None	N
P/M	0.9981	likely_pathogenic	0.9976	pathogenic	-1.137	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/N	0.9997	likely_pathogenic	0.9997	pathogenic	-1.863	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/Q	0.9987	likely_pathogenic	0.9987	pathogenic	-1.995	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/R	0.9975	likely_pathogenic	0.9978	pathogenic	-1.13	Destabilizing	1.0	D	0.831	deleterious	D	0.543710126	None	None	N
P/S	0.9947	likely_pathogenic	0.9937	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.765	deleterious	D	0.542696168	None	None	N
P/T	0.9919	likely_pathogenic	0.9907	pathogenic	-2.068	Highly Destabilizing	1.0	D	0.774	deleterious	D	0.555231015	None	None	N
P/V	0.9856	likely_pathogenic	0.9793	pathogenic	-1.138	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.509	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-1.201	Destabilizing	1.0	D	0.837	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.