TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30400	91423;91424;91425	chr2:178551702;178551701;178551700	chr2:179416429;179416428;179416427
N2AB	28759	86500;86501;86502	chr2:178551702;178551701;178551700	chr2:179416429;179416428;179416427
N2A	27832	83719;83720;83721	chr2:178551702;178551701;178551700	chr2:179416429;179416428;179416427
N2B	21335	64228;64229;64230	chr2:178551702;178551701;178551700	chr2:179416429;179416428;179416427
Novex-1	21460	64603;64604;64605	chr2:178551702;178551701;178551700	chr2:179416429;179416428;179416427
Novex-2	21527	64804;64805;64806	chr2:178551702;178551701;178551700	chr2:179416429;179416428;179416427
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-109
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1027
• 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
Y/C	rs376494747	-1.957	0.001	N	0.643	0.293	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.89E-06	0
Y/C	rs376494747	-1.957	0.001	N	0.643	0.293	None	gnomAD-4.0.0	1.36887E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99713E-07	1.16015E-05	0
Y/F	rs376494747	-1.663	None	N	0.307	0.063	0.170165803431	gnomAD-2.1.1	7.25E-05	None	None	None	None	N	None	0	2.9E-05	None	1.49432E-03	0	None	0	None	0	1.78E-05	0
Y/F	rs376494747	-1.663	None	N	0.307	0.063	0.170165803431	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	2.88018E-04	0	None	0	0	1.47E-05	0	0
Y/F	rs376494747	-1.663	None	N	0.307	0.063	0.170165803431	gnomAD-4.0.0	4.52495E-05	None	None	None	None	N	None	0	1.66795E-05	None	1.14919E-03	0	None	0	1.64528E-04	1.94998E-05	2.19698E-05	1.92184E-04
Y/H	rs753682966	None	0.484	N	0.694	0.308	0.353974658523	gnomAD-4.0.0	6.84418E-07	None	None	None	None	N	None	2.99079E-05	0	None	0	0	None	0	0	0	0	0
Y/N	rs753682966	-3.142	0.741	N	0.697	0.383	0.672318618897	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
Y/N	rs753682966	-3.142	0.741	N	0.697	0.383	0.672318618897	gnomAD-4.0.0	2.05325E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69906E-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
Y/A	0.3601	ambiguous	0.4334	ambiguous	-3.524	Highly Destabilizing	0.081	N	0.703	prob.neutral	None	None	None	None	N
Y/C	0.0833	likely_benign	0.1103	benign	-1.885	Destabilizing	0.001	N	0.643	neutral	N	0.489582834	None	None	N
Y/D	0.6113	likely_pathogenic	0.705	pathogenic	-3.42	Highly Destabilizing	0.741	D	0.715	prob.delet.	N	0.494486242	None	None	N
Y/E	0.7562	likely_pathogenic	0.8236	pathogenic	-3.285	Highly Destabilizing	0.555	D	0.691	prob.neutral	None	None	None	None	N
Y/F	0.0585	likely_benign	0.0587	benign	-1.447	Destabilizing	None	N	0.307	neutral	N	0.464820462	None	None	N
Y/G	0.4432	ambiguous	0.5344	ambiguous	-3.866	Highly Destabilizing	0.38	N	0.698	prob.neutral	None	None	None	None	N
Y/H	0.164	likely_benign	0.1917	benign	-2.21	Highly Destabilizing	0.484	N	0.694	prob.neutral	N	0.471609047	None	None	N
Y/I	0.2297	likely_benign	0.2842	benign	-2.388	Highly Destabilizing	0.081	N	0.669	neutral	None	None	None	None	N
Y/K	0.6229	likely_pathogenic	0.672	pathogenic	-2.245	Highly Destabilizing	0.555	D	0.686	prob.neutral	None	None	None	None	N
Y/L	0.3063	likely_benign	0.3659	ambiguous	-2.388	Highly Destabilizing	0.001	N	0.463	neutral	None	None	None	None	N
Y/M	0.3469	ambiguous	0.3956	ambiguous	-1.944	Destabilizing	0.38	N	0.676	prob.neutral	None	None	None	None	N
Y/N	0.244	likely_benign	0.308	benign	-2.74	Highly Destabilizing	0.741	D	0.697	prob.neutral	N	0.476381987	None	None	N
Y/P	0.9802	likely_pathogenic	0.9882	pathogenic	-2.779	Highly Destabilizing	0.791	D	0.727	prob.delet.	None	None	None	None	N
Y/Q	0.4293	ambiguous	0.5159	ambiguous	-2.674	Highly Destabilizing	0.791	D	0.687	prob.neutral	None	None	None	None	N
Y/R	0.3901	ambiguous	0.4672	ambiguous	-1.651	Destabilizing	0.555	D	0.697	prob.neutral	None	None	None	None	N
Y/S	0.1514	likely_benign	0.1814	benign	-3.123	Highly Destabilizing	0.317	N	0.684	prob.neutral	N	0.430265171	None	None	N
Y/T	0.2827	likely_benign	0.3379	benign	-2.897	Highly Destabilizing	0.38	N	0.683	prob.neutral	None	None	None	None	N
Y/V	0.2142	likely_benign	0.2635	benign	-2.779	Highly Destabilizing	0.081	N	0.689	prob.neutral	None	None	None	None	N
Y/W	0.3285	likely_benign	0.3562	ambiguous	-0.831	Destabilizing	0.824	D	0.689	prob.neutral	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.