TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33253	99982;99983;99984	chr2:178537450;178537449;178537448	chr2:179402177;179402176;179402175
N2AB	31612	95059;95060;95061	chr2:178537450;178537449;178537448	chr2:179402177;179402176;179402175
N2A	30685	92278;92279;92280	chr2:178537450;178537449;178537448	chr2:179402177;179402176;179402175
N2B	24188	72787;72788;72789	chr2:178537450;178537449;178537448	chr2:179402177;179402176;179402175
Novex-1	24313	73162;73163;73164	chr2:178537450;178537449;178537448	chr2:179402177;179402176;179402175
Novex-2	24380	73363;73364;73365	chr2:178537450;178537449;178537448	chr2:179402177;179402176;179402175
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-157
• Domain position: 51
• Structural Position: 137
• Q(SASA): 0.1909
• 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/P	None	None	1.0	N	0.776	0.589	0.620047664876	gnomAD-4.0.0	1.36901E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79945E-06	0	0
H/R	None	None	1.0	N	0.722	0.491	0.455722563999	gnomAD-4.0.0	1.36899E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79943E-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	0.924	likely_pathogenic	0.9117	pathogenic	-1.913	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	I
H/C	0.6559	likely_pathogenic	0.6396	pathogenic	-1.119	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
H/D	0.9348	likely_pathogenic	0.9105	pathogenic	-1.894	Destabilizing	1.0	D	0.686	prob.neutral	N	0.484380163	None	None	I
H/E	0.9599	likely_pathogenic	0.9436	pathogenic	-1.726	Destabilizing	1.0	D	0.552	neutral	None	None	None	None	I
H/F	0.7962	likely_pathogenic	0.7643	pathogenic	0.087	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
H/G	0.9668	likely_pathogenic	0.9594	pathogenic	-2.264	Highly Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
H/I	0.9052	likely_pathogenic	0.8869	pathogenic	-0.861	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
H/K	0.9555	likely_pathogenic	0.9281	pathogenic	-1.448	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
H/L	0.6413	likely_pathogenic	0.6247	pathogenic	-0.861	Destabilizing	1.0	D	0.761	deleterious	N	0.431855187	None	None	I
H/M	0.9205	likely_pathogenic	0.9161	pathogenic	-0.999	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
H/N	0.6386	likely_pathogenic	0.5831	pathogenic	-1.896	Destabilizing	1.0	D	0.549	neutral	N	0.465525043	None	None	I
H/P	0.9699	likely_pathogenic	0.9717	pathogenic	-1.206	Destabilizing	1.0	D	0.776	deleterious	N	0.503659357	None	None	I
H/Q	0.8809	likely_pathogenic	0.8462	pathogenic	-1.493	Destabilizing	1.0	D	0.76	deleterious	N	0.450094231	None	None	I
H/R	0.8525	likely_pathogenic	0.7714	pathogenic	-1.73	Destabilizing	1.0	D	0.722	prob.delet.	N	0.449574156	None	None	I
H/S	0.8366	likely_pathogenic	0.8109	pathogenic	-1.987	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
H/T	0.9184	likely_pathogenic	0.9009	pathogenic	-1.728	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
H/V	0.8678	likely_pathogenic	0.8424	pathogenic	-1.206	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
H/W	0.8493	likely_pathogenic	0.8044	pathogenic	0.497	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
H/Y	0.4802	ambiguous	0.3944	ambiguous	0.226	Stabilizing	1.0	D	0.583	neutral	N	0.466314477	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.