TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24764	74515;74516;74517	chr2:178571842;178571841;178571840	chr2:179436569;179436568;179436567
N2AB	23123	69592;69593;69594	chr2:178571842;178571841;178571840	chr2:179436569;179436568;179436567
N2A	22196	66811;66812;66813	chr2:178571842;178571841;178571840	chr2:179436569;179436568;179436567
N2B	15699	47320;47321;47322	chr2:178571842;178571841;178571840	chr2:179436569;179436568;179436567
Novex-1	15824	47695;47696;47697	chr2:178571842;178571841;178571840	chr2:179436569;179436568;179436567
Novex-2	15891	47896;47897;47898	chr2:178571842;178571841;178571840	chr2:179436569;179436568;179436567
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: Ig-133
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3862
• 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/E	None	None	0.007	N	0.28	0.197	0.39843156188	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85928E-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	0.3116	likely_benign	0.3203	benign	-1.158	Destabilizing	0.996	D	0.462	neutral	None	None	None	None	N
A/D	0.5661	likely_pathogenic	0.5815	pathogenic	-1.167	Destabilizing	0.59	D	0.514	neutral	None	None	None	None	N
A/E	0.4376	ambiguous	0.4228	ambiguous	-1.107	Destabilizing	0.007	N	0.28	neutral	N	0.50173656	None	None	N
A/F	0.2345	likely_benign	0.2421	benign	-0.896	Destabilizing	0.91	D	0.57	neutral	None	None	None	None	N
A/G	0.1971	likely_benign	0.2055	benign	-1.325	Destabilizing	0.684	D	0.365	neutral	N	0.486652464	None	None	N
A/H	0.518	ambiguous	0.5274	ambiguous	-1.535	Destabilizing	0.987	D	0.555	neutral	None	None	None	None	N
A/I	0.1562	likely_benign	0.1633	benign	-0.085	Destabilizing	0.009	N	0.273	neutral	None	None	None	None	N
A/K	0.6001	likely_pathogenic	0.6011	pathogenic	-1.089	Destabilizing	0.59	D	0.444	neutral	None	None	None	None	N
A/L	0.1763	likely_benign	0.1874	benign	-0.085	Destabilizing	0.17	N	0.38	neutral	None	None	None	None	N
A/M	0.1846	likely_benign	0.1909	benign	-0.242	Destabilizing	0.91	D	0.501	neutral	None	None	None	None	N
A/N	0.4063	ambiguous	0.424	ambiguous	-0.994	Destabilizing	0.91	D	0.56	neutral	None	None	None	None	N
A/P	0.6577	likely_pathogenic	0.7136	pathogenic	-0.333	Destabilizing	0.939	D	0.515	neutral	N	0.486825822	None	None	N
A/Q	0.4693	ambiguous	0.4702	ambiguous	-1.005	Destabilizing	0.835	D	0.516	neutral	None	None	None	None	N
A/R	0.5218	ambiguous	0.5243	ambiguous	-0.959	Destabilizing	0.91	D	0.513	neutral	None	None	None	None	N
A/S	0.1142	likely_benign	0.1182	benign	-1.483	Destabilizing	0.078	N	0.258	neutral	N	0.482630724	None	None	N
A/T	0.0859	likely_benign	0.0884	benign	-1.293	Destabilizing	0.028	N	0.256	neutral	N	0.425179931	None	None	N
A/V	0.0873	likely_benign	0.0902	benign	-0.333	Destabilizing	0.028	N	0.138	neutral	N	0.350657955	None	None	N
A/W	0.6331	likely_pathogenic	0.6571	pathogenic	-1.335	Destabilizing	0.996	D	0.65	neutral	None	None	None	None	N
A/Y	0.357	ambiguous	0.3758	ambiguous	-0.858	Destabilizing	0.953	D	0.573	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.