TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27970	84133;84134;84135	chr2:178562224;178562223;178562222	chr2:179426951;179426950;179426949
N2AB	26329	79210;79211;79212	chr2:178562224;178562223;178562222	chr2:179426951;179426950;179426949
N2A	25402	76429;76430;76431	chr2:178562224;178562223;178562222	chr2:179426951;179426950;179426949
N2B	18905	56938;56939;56940	chr2:178562224;178562223;178562222	chr2:179426951;179426950;179426949
Novex-1	19030	57313;57314;57315	chr2:178562224;178562223;178562222	chr2:179426951;179426950;179426949
Novex-2	19097	57514;57515;57516	chr2:178562224;178562223;178562222	chr2:179426951;179426950;179426949
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-142
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5662
• 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
H/R	None	None	0.007	N	0.265	0.088	0.152612264143	gnomAD-4.0.0	1.59421E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86136E-06	0	0
H/Y	None	None	0.039	N	0.356	0.106	0.168933306366	gnomAD-4.0.0	1.59439E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86159E-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
H/A	0.1767	likely_benign	0.1523	benign	-0.515	Destabilizing	0.001	N	0.329	neutral	None	None	None	None	I
H/C	0.1533	likely_benign	0.1458	benign	0.064	Stabilizing	0.316	N	0.467	neutral	None	None	None	None	I
H/D	0.1289	likely_benign	0.1199	benign	-0.553	Destabilizing	None	N	0.185	neutral	N	0.403399149	None	None	I
H/E	0.2543	likely_benign	0.2173	benign	-0.44	Destabilizing	0.001	N	0.249	neutral	None	None	None	None	I
H/F	0.3208	likely_benign	0.2813	benign	0.882	Stabilizing	0.041	N	0.503	neutral	None	None	None	None	I
H/G	0.1887	likely_benign	0.1722	benign	-0.896	Destabilizing	0.001	N	0.303	neutral	None	None	None	None	I
H/I	0.2729	likely_benign	0.2332	benign	0.538	Stabilizing	0.018	N	0.509	neutral	None	None	None	None	I
H/K	0.2075	likely_benign	0.1751	benign	-0.377	Destabilizing	0.001	N	0.348	neutral	None	None	None	None	I
H/L	0.1114	likely_benign	0.1058	benign	0.538	Stabilizing	0.003	N	0.468	neutral	N	0.471066936	None	None	I
H/M	0.3614	ambiguous	0.3181	benign	0.202	Stabilizing	0.316	N	0.477	neutral	None	None	None	None	I
H/N	0.0499	likely_benign	0.0498	benign	-0.703	Destabilizing	None	N	0.125	neutral	N	0.342966766	None	None	I
H/P	0.1265	likely_benign	0.1174	benign	0.208	Stabilizing	0.013	N	0.401	neutral	N	0.43048975	None	None	I
H/Q	0.1431	likely_benign	0.1257	benign	-0.432	Destabilizing	0.007	N	0.269	neutral	N	0.387448262	None	None	I
H/R	0.1122	likely_benign	0.1035	benign	-0.982	Destabilizing	0.007	N	0.265	neutral	N	0.418789889	None	None	I
H/S	0.1063	likely_benign	0.0952	benign	-0.669	Destabilizing	None	N	0.177	neutral	None	None	None	None	I
H/T	0.1291	likely_benign	0.1114	benign	-0.436	Destabilizing	0.001	N	0.393	neutral	None	None	None	None	I
H/V	0.2114	likely_benign	0.1808	benign	0.208	Stabilizing	0.009	N	0.449	neutral	None	None	None	None	I
H/W	0.5091	ambiguous	0.4708	ambiguous	1.208	Stabilizing	0.635	D	0.425	neutral	None	None	None	None	I
H/Y	0.1016	likely_benign	0.0956	benign	1.221	Stabilizing	0.039	N	0.356	neutral	N	0.471240294	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.