TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25517	76774;76775;76776	chr2:178569583;178569582;178569581	chr2:179434310;179434309;179434308
N2AB	23876	71851;71852;71853	chr2:178569583;178569582;178569581	chr2:179434310;179434309;179434308
N2A	22949	69070;69071;69072	chr2:178569583;178569582;178569581	chr2:179434310;179434309;179434308
N2B	16452	49579;49580;49581	chr2:178569583;178569582;178569581	chr2:179434310;179434309;179434308
Novex-1	16577	49954;49955;49956	chr2:178569583;178569582;178569581	chr2:179434310;179434309;179434308
Novex-2	16644	50155;50156;50157	chr2:178569583;178569582;178569581	chr2:179434310;179434309;179434308
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-135
• Domain position: 4
• Structural Position: 8
• Q(SASA): 0.7279
• Predicted PPI site: I

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
R/G	rs780584058	None	0.969	N	0.529	0.357	0.5452609689	gnomAD-4.0.0	2.05375E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.48092E-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
R/A	0.9423	likely_pathogenic	0.9431	pathogenic	0.144	Stabilizing	0.953	D	0.57	neutral	None	None	None	None	I
R/C	0.5896	likely_pathogenic	0.6071	pathogenic	-0.152	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	I
R/D	0.984	likely_pathogenic	0.9843	pathogenic	-0.188	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	I
R/E	0.8999	likely_pathogenic	0.8992	pathogenic	-0.127	Destabilizing	0.976	D	0.596	neutral	None	None	None	None	I
R/F	0.9699	likely_pathogenic	0.971	pathogenic	-0.134	Destabilizing	0.986	D	0.668	neutral	None	None	None	None	I
R/G	0.8034	likely_pathogenic	0.8085	pathogenic	-0.026	Destabilizing	0.969	D	0.529	neutral	N	0.514257566	None	None	I
R/H	0.4183	ambiguous	0.433	ambiguous	-0.579	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	I
R/I	0.9237	likely_pathogenic	0.9238	pathogenic	0.549	Stabilizing	0.973	D	0.655	neutral	None	None	None	None	I
R/K	0.2781	likely_benign	0.2803	benign	-0.003	Destabilizing	0.863	D	0.596	neutral	N	0.484913307	None	None	I
R/L	0.8153	likely_pathogenic	0.8339	pathogenic	0.549	Stabilizing	0.778	D	0.553	neutral	None	None	None	None	I
R/M	0.869	likely_pathogenic	0.8694	pathogenic	0.009	Stabilizing	0.76	D	0.455	neutral	N	0.488335675	None	None	I
R/N	0.9649	likely_pathogenic	0.9628	pathogenic	0.065	Stabilizing	0.998	D	0.602	neutral	None	None	None	None	I
R/P	0.9698	likely_pathogenic	0.9777	pathogenic	0.433	Stabilizing	0.998	D	0.637	neutral	None	None	None	None	I
R/Q	0.3067	likely_benign	0.2967	benign	0.045	Stabilizing	0.993	D	0.599	neutral	None	None	None	None	I
R/S	0.9586	likely_pathogenic	0.957	pathogenic	-0.135	Destabilizing	0.969	D	0.558	neutral	N	0.489421631	None	None	I
R/T	0.91	likely_pathogenic	0.9057	pathogenic	0.048	Stabilizing	0.939	D	0.559	neutral	N	0.494194571	None	None	I
R/V	0.9335	likely_pathogenic	0.9346	pathogenic	0.433	Stabilizing	0.91	D	0.568	neutral	None	None	None	None	I
R/W	0.6403	likely_pathogenic	0.6532	pathogenic	-0.305	Destabilizing	0.999	D	0.694	prob.neutral	N	0.5153407	None	None	I
R/Y	0.8927	likely_pathogenic	0.8957	pathogenic	0.123	Stabilizing	0.993	D	0.639	neutral	None	None	None	None	I

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.