TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24056	72391;72392;72393	chr2:178573966;178573965;178573964	chr2:179438693;179438692;179438691
N2AB	22415	67468;67469;67470	chr2:178573966;178573965;178573964	chr2:179438693;179438692;179438691
N2A	21488	64687;64688;64689	chr2:178573966;178573965;178573964	chr2:179438693;179438692;179438691
N2B	14991	45196;45197;45198	chr2:178573966;178573965;178573964	chr2:179438693;179438692;179438691
Novex-1	15116	45571;45572;45573	chr2:178573966;178573965;178573964	chr2:179438693;179438692;179438691
Novex-2	15183	45772;45773;45774	chr2:178573966;178573965;178573964	chr2:179438693;179438692;179438691
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-131
• Domain position: 28
• Structural Position: 41
• Q(SASA): 0.7504
• 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
R/C	rs372662393	-0.19	1.0	D	0.669	0.462	None	gnomAD-2.1.1	3.58E-05	None	None	None	None	I	None	1.65453E-04	0	None	0	1.03681E-04	None	0	None	0	1.57E-05	2.81215E-04
R/C	rs372662393	-0.19	1.0	D	0.669	0.462	None	gnomAD-3.1.2	1.05263E-04	None	None	None	None	I	None	2.657E-04	1.31096E-04	0	0	0	None	0	0	2.94E-05	2.07641E-04	0
R/C	rs372662393	-0.19	1.0	D	0.669	0.462	None	gnomAD-4.0.0	2.29346E-05	None	None	None	None	I	None	2.53414E-04	3.33467E-05	None	0	4.47648E-05	None	0	0	8.47751E-06	2.1966E-05	3.20195E-05
R/G	None	None	0.975	N	0.565	0.396	0.714588635789	gnomAD-4.0.0	1.36877E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79918E-06	0	0
R/H	rs398124455	-0.547	0.999	N	0.627	0.297	0.371903410333	gnomAD-2.1.1	2.54087E-04	None	None	None	None	I	None	0	0	None	0	5.19E-05	None	2.2244E-03	None	0	7.83E-06	1.40726E-04
R/H	rs398124455	-0.547	0.999	N	0.627	0.297	0.371903410333	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	1.24378E-03	0
R/H	rs398124455	-0.547	0.999	N	0.627	0.297	0.371903410333	gnomAD-4.0.0	1.43185E-04	None	None	None	None	I	None	0	0	None	0	2.23784E-05	None	1.56255E-05	0	1.35644E-05	2.24053E-03	1.44097E-04
R/L	rs398124455	0.345	0.975	N	0.565	0.366	0.669087604336	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/L	rs398124455	0.345	0.975	N	0.565	0.366	0.669087604336	gnomAD-4.0.0	3.42202E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49805E-06	0	0
R/S	rs372662393	None	0.975	N	0.631	0.278	0.464270400615	gnomAD-4.0.0	7.52824E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.8955E-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
R/A	0.7161	likely_pathogenic	0.7151	pathogenic	0.128	Stabilizing	0.953	D	0.631	neutral	None	None	None	None	I
R/C	0.2135	likely_benign	0.2357	benign	-0.219	Destabilizing	1.0	D	0.669	neutral	D	0.525219429	None	None	I
R/D	0.9186	likely_pathogenic	0.912	pathogenic	-0.249	Destabilizing	0.986	D	0.582	neutral	None	None	None	None	I
R/E	0.6701	likely_pathogenic	0.6728	pathogenic	-0.195	Destabilizing	0.91	D	0.635	neutral	None	None	None	None	I
R/F	0.6253	likely_pathogenic	0.6181	pathogenic	-0.199	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	I
R/G	0.6509	likely_pathogenic	0.6376	pathogenic	-0.024	Destabilizing	0.975	D	0.565	neutral	N	0.506861685	None	None	I
R/H	0.123	likely_benign	0.1321	benign	-0.61	Destabilizing	0.999	D	0.627	neutral	N	0.515049787	None	None	I
R/I	0.2962	likely_benign	0.2958	benign	0.483	Stabilizing	0.993	D	0.62	neutral	None	None	None	None	I
R/K	0.124	likely_benign	0.1256	benign	-0.065	Destabilizing	0.06	N	0.405	neutral	None	None	None	None	I
R/L	0.3236	likely_benign	0.3125	benign	0.483	Stabilizing	0.975	D	0.565	neutral	N	0.51470307	None	None	I
R/M	0.4093	ambiguous	0.4023	ambiguous	-0.052	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	I
R/N	0.765	likely_pathogenic	0.7584	pathogenic	-0.045	Destabilizing	0.986	D	0.602	neutral	None	None	None	None	I
R/P	0.9712	likely_pathogenic	0.9681	pathogenic	0.384	Stabilizing	0.996	D	0.595	neutral	N	0.513863124	None	None	I
R/Q	0.1298	likely_benign	0.1414	benign	-0.043	Destabilizing	0.986	D	0.601	neutral	None	None	None	None	I
R/S	0.7283	likely_pathogenic	0.7223	pathogenic	-0.202	Destabilizing	0.975	D	0.631	neutral	N	0.494095724	None	None	I
R/T	0.5009	ambiguous	0.4791	ambiguous	-0.031	Destabilizing	0.986	D	0.579	neutral	None	None	None	None	I
R/V	0.4555	ambiguous	0.4612	ambiguous	0.384	Stabilizing	0.993	D	0.603	neutral	None	None	None	None	I
R/W	0.2698	likely_benign	0.2803	benign	-0.408	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
R/Y	0.4408	ambiguous	0.4516	ambiguous	0.022	Stabilizing	0.998	D	0.608	neutral	None	None	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.