TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30882	92869;92870;92871	chr2:178548982;178548981;178548980	chr2:179413709;179413708;179413707
N2AB	29241	87946;87947;87948	chr2:178548982;178548981;178548980	chr2:179413709;179413708;179413707
N2A	28314	85165;85166;85167	chr2:178548982;178548981;178548980	chr2:179413709;179413708;179413707
N2B	21817	65674;65675;65676	chr2:178548982;178548981;178548980	chr2:179413709;179413708;179413707
Novex-1	21942	66049;66050;66051	chr2:178548982;178548981;178548980	chr2:179413709;179413708;179413707
Novex-2	22009	66250;66251;66252	chr2:178548982;178548981;178548980	chr2:179413709;179413708;179413707
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-113
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.2904
• 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
T/R	None	None	0.241	N	0.32	0.286	0.388174495139	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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
T/A	0.1166	likely_benign	0.1136	benign	-0.811	Destabilizing	0.948	D	0.481	neutral	N	0.484138031	None	None	N
T/C	0.4368	ambiguous	0.4362	ambiguous	-0.483	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
T/D	0.6221	likely_pathogenic	0.5993	pathogenic	0.284	Stabilizing	0.998	D	0.631	neutral	None	None	None	None	N
T/E	0.4272	ambiguous	0.4001	ambiguous	0.283	Stabilizing	0.995	D	0.601	neutral	None	None	None	None	N
T/F	0.3814	ambiguous	0.3874	ambiguous	-0.998	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
T/G	0.4783	ambiguous	0.4784	ambiguous	-1.047	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
T/H	0.3717	ambiguous	0.3542	ambiguous	-1.28	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/I	0.1443	likely_benign	0.1455	benign	-0.278	Destabilizing	0.956	D	0.547	neutral	N	0.495645694	None	None	N
T/K	0.3183	likely_benign	0.2886	benign	-0.483	Destabilizing	0.956	D	0.549	neutral	N	0.473742777	None	None	N
T/L	0.1347	likely_benign	0.1348	benign	-0.278	Destabilizing	0.967	D	0.501	neutral	None	None	None	None	N
T/M	0.0918	likely_benign	0.0954	benign	-0.077	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
T/N	0.2253	likely_benign	0.2166	benign	-0.45	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
T/P	0.3606	ambiguous	0.3455	ambiguous	-0.424	Destabilizing	0.999	D	0.637	neutral	N	0.49831872	None	None	N
T/Q	0.2992	likely_benign	0.2808	benign	-0.57	Destabilizing	0.995	D	0.642	neutral	None	None	None	None	N
T/R	0.2664	likely_benign	0.2505	benign	-0.313	Destabilizing	0.241	N	0.32	neutral	N	0.478377586	None	None	N
T/S	0.1773	likely_benign	0.1751	benign	-0.795	Destabilizing	0.989	D	0.449	neutral	N	0.474578924	None	None	N
T/V	0.1083	likely_benign	0.1115	benign	-0.424	Destabilizing	0.437	N	0.367	neutral	None	None	None	None	N
T/W	0.7668	likely_pathogenic	0.767	pathogenic	-0.919	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
T/Y	0.4643	ambiguous	0.4642	ambiguous	-0.668	Destabilizing	0.999	D	0.729	prob.delet.	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.