TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28495	85708;85709;85710	chr2:178560649;178560648;178560647	chr2:179425376;179425375;179425374
N2AB	26854	80785;80786;80787	chr2:178560649;178560648;178560647	chr2:179425376;179425375;179425374
N2A	25927	78004;78005;78006	chr2:178560649;178560648;178560647	chr2:179425376;179425375;179425374
N2B	19430	58513;58514;58515	chr2:178560649;178560648;178560647	chr2:179425376;179425375;179425374
Novex-1	19555	58888;58889;58890	chr2:178560649;178560648;178560647	chr2:179425376;179425375;179425374
Novex-2	19622	59089;59090;59091	chr2:178560649;178560648;178560647	chr2:179425376;179425375;179425374
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-95
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.4842
• 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/L	rs554119186	0.492	0.006	N	0.287	0.106	0.242244723065	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	1.66058E-04
H/L	rs554119186	0.492	0.006	N	0.287	0.106	0.242244723065	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	0	4.58535E-04	0	0	0	None	0	0	1.47E-05	0	0
H/L	rs554119186	0.492	0.006	N	0.287	0.106	0.242244723065	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
H/L	rs554119186	0.492	0.006	N	0.287	0.106	0.242244723065	gnomAD-4.0.0	1.40926E-05	None	None	None	None	I	None	0	1.69457E-04	None	0	0	None	0	0	2.39308E-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	0.6708	likely_pathogenic	0.6687	pathogenic	0.225	Stabilizing	0.002	N	0.257	neutral	None	None	None	None	I
H/C	0.2271	likely_benign	0.2093	benign	0.562	Stabilizing	0.497	N	0.279	neutral	None	None	None	None	I
H/D	0.7178	likely_pathogenic	0.741	pathogenic	0.084	Stabilizing	0.014	N	0.313	neutral	N	0.413327275	None	None	I
H/E	0.7229	likely_pathogenic	0.7357	pathogenic	0.092	Stabilizing	0.002	N	0.131	neutral	None	None	None	None	I
H/F	0.6359	likely_pathogenic	0.6285	pathogenic	0.739	Stabilizing	0.085	N	0.293	neutral	None	None	None	None	I
H/G	0.5289	ambiguous	0.5417	ambiguous	-0.023	Destabilizing	0.008	N	0.253	neutral	None	None	None	None	I
H/I	0.7767	likely_pathogenic	0.7721	pathogenic	0.843	Stabilizing	0.085	N	0.345	neutral	None	None	None	None	I
H/K	0.2836	likely_benign	0.3116	benign	0.197	Stabilizing	None	N	0.084	neutral	None	None	None	None	I
H/L	0.2834	likely_benign	0.2738	benign	0.843	Stabilizing	0.006	N	0.287	neutral	N	0.46970342	None	None	I
H/M	0.8048	likely_pathogenic	0.7973	pathogenic	0.641	Stabilizing	0.497	N	0.309	neutral	None	None	None	None	I
H/N	0.3896	ambiguous	0.4326	ambiguous	0.225	Stabilizing	0.006	N	0.121	neutral	N	0.414367425	None	None	I
H/P	0.7334	likely_pathogenic	0.6791	pathogenic	0.662	Stabilizing	0.028	N	0.25	neutral	N	0.442786178	None	None	I
H/Q	0.3048	likely_benign	0.2738	benign	0.283	Stabilizing	0.003	N	0.147	neutral	N	0.449904151	None	None	I
H/R	0.0532	likely_benign	0.0497	benign	-0.25	Destabilizing	None	N	0.04	neutral	N	0.297697757	None	None	I
H/S	0.5611	ambiguous	0.5784	pathogenic	0.243	Stabilizing	0.008	N	0.235	neutral	None	None	None	None	I
H/T	0.6888	likely_pathogenic	0.7092	pathogenic	0.348	Stabilizing	0.008	N	0.285	neutral	None	None	None	None	I
H/V	0.6636	likely_pathogenic	0.6677	pathogenic	0.662	Stabilizing	0.018	N	0.268	neutral	None	None	None	None	I
H/W	0.4697	ambiguous	0.4579	ambiguous	0.708	Stabilizing	0.497	N	0.263	neutral	None	None	None	None	I
H/Y	0.2255	likely_benign	0.2178	benign	1.01	Stabilizing	0.028	N	0.183	neutral	N	0.469876778	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.