TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14836	44731;44732;44733	chr2:178625315;178625314;178625313	chr2:179490042;179490041;179490040
N2AB	13195	39808;39809;39810	chr2:178625315;178625314;178625313	chr2:179490042;179490041;179490040
N2A	12268	37027;37028;37029	chr2:178625315;178625314;178625313	chr2:179490042;179490041;179490040
N2B	5771	17536;17537;17538	chr2:178625315;178625314;178625313	chr2:179490042;179490041;179490040
Novex-1	5896	17911;17912;17913	chr2:178625315;178625314;178625313	chr2:179490042;179490041;179490040
Novex-2	5963	18112;18113;18114	chr2:178625315;178625314;178625313	chr2:179490042;179490041;179490040
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: Ig-99
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.2167
• 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/A	rs761382291	-1.377	0.027	N	0.53	0.1	0.19670166235	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
T/A	rs761382291	-1.377	0.027	N	0.53	0.1	0.19670166235	gnomAD-4.0.0	6.00167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56258E-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	0.0984	likely_benign	0.1034	benign	-1.196	Destabilizing	0.027	N	0.53	neutral	N	0.505198093	None	None	N
T/C	0.4103	ambiguous	0.4248	ambiguous	-0.829	Destabilizing	0.824	D	0.625	neutral	None	None	None	None	N
T/D	0.4892	ambiguous	0.5341	ambiguous	-1.357	Destabilizing	0.38	N	0.623	neutral	None	None	None	None	N
T/E	0.2806	likely_benign	0.2956	benign	-1.157	Destabilizing	0.081	N	0.601	neutral	None	None	None	None	N
T/F	0.2062	likely_benign	0.214	benign	-0.76	Destabilizing	0.38	N	0.745	deleterious	None	None	None	None	N
T/G	0.3235	likely_benign	0.3283	benign	-1.608	Destabilizing	0.149	N	0.673	neutral	None	None	None	None	N
T/H	0.2069	likely_benign	0.2285	benign	-1.649	Destabilizing	0.824	D	0.717	prob.delet.	None	None	None	None	N
T/I	0.1146	likely_benign	0.1206	benign	-0.113	Destabilizing	0.022	N	0.604	neutral	N	0.511456543	None	None	N
T/K	0.1406	likely_benign	0.1437	benign	-0.521	Destabilizing	0.062	N	0.603	neutral	N	0.504046797	None	None	N
T/L	0.085	likely_benign	0.0895	benign	-0.113	Destabilizing	0.081	N	0.602	neutral	None	None	None	None	N
T/M	0.0795	likely_benign	0.0808	benign	-0.227	Destabilizing	0.38	N	0.641	neutral	None	None	None	None	N
T/N	0.1689	likely_benign	0.1931	benign	-1.131	Destabilizing	0.38	N	0.589	neutral	None	None	None	None	N
T/P	0.5797	likely_pathogenic	0.6721	pathogenic	-0.444	Destabilizing	0.484	N	0.654	neutral	D	0.634033351	None	None	N
T/Q	0.1655	likely_benign	0.1707	benign	-0.917	Destabilizing	0.235	N	0.653	neutral	None	None	None	None	N
T/R	0.0931	likely_benign	0.0964	benign	-0.724	Destabilizing	0.001	N	0.403	neutral	N	0.510170285	None	None	N
T/S	0.152	likely_benign	0.1586	benign	-1.38	Destabilizing	0.005	N	0.361	neutral	N	0.508867805	None	None	N
T/V	0.104	likely_benign	0.1023	benign	-0.444	Destabilizing	0.001	N	0.271	neutral	None	None	None	None	N
T/W	0.4841	ambiguous	0.4819	ambiguous	-0.894	Destabilizing	0.935	D	0.751	deleterious	None	None	None	None	N
T/Y	0.276	likely_benign	0.2869	benign	-0.524	Destabilizing	0.555	D	0.741	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.