TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15643	47152;47153;47154	chr2:178618623;178618622;178618621	chr2:179483350;179483349;179483348
N2AB	14002	42229;42230;42231	chr2:178618623;178618622;178618621	chr2:179483350;179483349;179483348
N2A	13075	39448;39449;39450	chr2:178618623;178618622;178618621	chr2:179483350;179483349;179483348
N2B	6578	19957;19958;19959	chr2:178618623;178618622;178618621	chr2:179483350;179483349;179483348
Novex-1	6703	20332;20333;20334	chr2:178618623;178618622;178618621	chr2:179483350;179483349;179483348
Novex-2	6770	20533;20534;20535	chr2:178618623;178618622;178618621	chr2:179483350;179483349;179483348
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-108
• Domain position: 76
• Structural Position: 163
• Q(SASA): 0.9639
• 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/Q	rs770655963	0.282	0.995	N	0.535	0.253	0.394384168047	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
H/Q	rs770655963	0.282	0.995	N	0.535	0.253	0.394384168047	gnomAD-4.0.0	2.73946E-06	None	None	None	None	I	None	0	8.96982E-05	None	0	0	None	0	0	0	0	0
H/R	rs368502650	0.045	0.984	N	0.52	0.508	None	gnomAD-2.1.1	2.184E-04	None	None	None	None	I	None	1.65549E-04	3.97682E-04	None	1.25896E-03	0	None	0	None	0	2.19315E-04	2.81532E-04
H/R	rs368502650	0.045	0.984	N	0.52	0.508	None	gnomAD-3.1.2	2.36904E-04	None	None	None	None	I	None	7.24E-05	4.59318E-04	0	1.7311E-03	0	None	0	0	2.94516E-04	0	0
H/R	rs368502650	0.045	0.984	N	0.52	0.508	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
H/R	rs368502650	0.045	0.984	N	0.52	0.508	None	gnomAD-4.0.0	2.72903E-04	None	None	None	None	I	None	1.06806E-04	3.67438E-04	None	1.28613E-03	0	None	0	0	2.87527E-04	0	5.2888E-04

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	0.5172	ambiguous	0.588	pathogenic	0.571	Stabilizing	0.919	D	0.587	neutral	None	None	None	None	I
H/C	0.275	likely_benign	0.3557	ambiguous	0.783	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	I
H/D	0.6004	likely_pathogenic	0.6622	pathogenic	-0.157	Destabilizing	0.995	D	0.538	neutral	N	0.504327812	None	None	I
H/E	0.6157	likely_pathogenic	0.6618	pathogenic	-0.152	Destabilizing	0.959	D	0.525	neutral	None	None	None	None	I
H/F	0.2115	likely_benign	0.245	benign	1.068	Stabilizing	0.952	D	0.523	neutral	None	None	None	None	I
H/G	0.6412	likely_pathogenic	0.7181	pathogenic	0.34	Stabilizing	0.959	D	0.541	neutral	None	None	None	None	I
H/I	0.4838	ambiguous	0.5669	pathogenic	1.14	Stabilizing	0.976	D	0.629	neutral	None	None	None	None	I
H/K	0.6335	likely_pathogenic	0.6569	pathogenic	0.477	Stabilizing	0.988	D	0.519	neutral	None	None	None	None	I
H/L	0.2374	likely_benign	0.2876	benign	1.14	Stabilizing	0.811	D	0.555	neutral	N	0.496986948	None	None	I
H/M	0.6428	likely_pathogenic	0.6992	pathogenic	0.805	Stabilizing	0.999	D	0.634	neutral	None	None	None	None	I
H/N	0.1982	likely_benign	0.2261	benign	0.393	Stabilizing	0.946	D	0.52	neutral	N	0.50411833	None	None	I
H/P	0.8205	likely_pathogenic	0.8541	pathogenic	0.975	Stabilizing	0.995	D	0.62	neutral	N	0.504327812	None	None	I
H/Q	0.4139	ambiguous	0.4746	ambiguous	0.455	Stabilizing	0.995	D	0.535	neutral	N	0.505176181	None	None	I
H/R	0.346	ambiguous	0.3823	ambiguous	-0.073	Destabilizing	0.984	D	0.52	neutral	N	0.50411833	None	None	I
H/S	0.4704	ambiguous	0.5448	ambiguous	0.564	Stabilizing	0.959	D	0.529	neutral	None	None	None	None	I
H/T	0.5949	likely_pathogenic	0.6616	pathogenic	0.662	Stabilizing	0.988	D	0.579	neutral	None	None	None	None	I
H/V	0.4081	ambiguous	0.4733	ambiguous	0.975	Stabilizing	0.976	D	0.587	neutral	None	None	None	None	I
H/W	0.3985	ambiguous	0.4365	ambiguous	0.935	Stabilizing	0.997	D	0.639	neutral	None	None	None	None	I
H/Y	0.0706	likely_benign	0.0811	benign	1.235	Stabilizing	0.026	N	0.373	neutral	N	0.502448275	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.