TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30628	92107;92108;92109	chr2:178549840;178549839;178549838	chr2:179414567;179414566;179414565
N2AB	28987	87184;87185;87186	chr2:178549840;178549839;178549838	chr2:179414567;179414566;179414565
N2A	28060	84403;84404;84405	chr2:178549840;178549839;178549838	chr2:179414567;179414566;179414565
N2B	21563	64912;64913;64914	chr2:178549840;178549839;178549838	chr2:179414567;179414566;179414565
Novex-1	21688	65287;65288;65289	chr2:178549840;178549839;178549838	chr2:179414567;179414566;179414565
Novex-2	21755	65488;65489;65490	chr2:178549840;178549839;178549838	chr2:179414567;179414566;179414565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-111
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.684
• 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
R/I	rs780476250	0.4	1.0	N	0.787	0.361	0.494700469353	gnomAD-2.1.1	4.38E-06	None	None	None	None	N	None	0	3.28E-05	None	0	0	None	0	None	0	0	0
R/I	rs780476250	0.4	1.0	N	0.787	0.361	0.494700469353	gnomAD-4.0.0	1.39727E-06	None	None	None	None	N	None	0	4.92756E-05	None	0	0	None	0	0	0	0	0
R/K	rs780476250	-0.086	0.997	N	0.529	0.22	None	gnomAD-2.1.1	1.32E-05	None	None	None	None	N	None	6.6E-05	0	None	0	0	None	7.91E-05	None	0	0	0
R/K	rs780476250	-0.086	0.997	N	0.529	0.22	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.44781E-04	0	0	0	0	None	0	0	0	0	0
R/K	rs780476250	-0.086	0.997	N	0.529	0.22	None	gnomAD-4.0.0	1.3892E-05	None	None	None	None	N	None	2.30659E-04	0	None	0	0	None	0	0	0	2.33242E-05	4.91884E-05
R/S	rs144922355	-0.428	1.0	N	0.766	0.339	0.257786959452	gnomAD-2.1.1	1.65515E-03	None	None	None	None	N	None	1.75468E-02	3.40136E-04	None	0	0	None	7.58E-05	None	0	1.63E-05	3.00842E-04
R/S	rs144922355	-0.428	1.0	N	0.766	0.339	0.257786959452	gnomAD-3.1.2	4.54109E-03	None	None	None	None	N	None	1.62225E-02	6.55308E-04	0	0	0	None	0	0	1.47E-05	0	3.82044E-03
R/S	rs144922355	-0.428	1.0	N	0.766	0.339	0.257786959452	1000 genomes	3.99361E-03	None	None	None	None	N	None	1.51E-02	0	None	None	0	0	None	None	None	0	None
R/S	rs144922355	-0.428	1.0	N	0.766	0.339	0.257786959452	gnomAD-4.0.0	8.43089E-04	None	None	None	None	N	None	1.66265E-02	4.92247E-04	None	0	0	None	0	3.36927E-04	6.85964E-06	4.60872E-05	1.11122E-03

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	0.3718	ambiguous	0.5212	ambiguous	-0.647	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
R/C	0.1229	likely_benign	0.1737	benign	-0.568	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
R/D	0.6057	likely_pathogenic	0.7555	pathogenic	-0.076	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
R/E	0.3374	likely_benign	0.4589	ambiguous	0.1	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
R/F	0.4667	ambiguous	0.6304	pathogenic	-0.17	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
R/G	0.291	likely_benign	0.4461	ambiguous	-1.01	Destabilizing	1.0	D	0.699	prob.neutral	N	0.515595999	None	None	N
R/H	0.0766	likely_benign	0.102	benign	-1.363	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
R/I	0.2244	likely_benign	0.3244	benign	0.348	Stabilizing	1.0	D	0.787	deleterious	N	0.498626392	None	None	N
R/K	0.1103	likely_benign	0.1318	benign	-0.543	Destabilizing	0.997	D	0.529	neutral	N	0.411177978	None	None	N
R/L	0.2015	likely_benign	0.2972	benign	0.348	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
R/M	0.288	likely_benign	0.4069	ambiguous	-0.204	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
R/N	0.4313	ambiguous	0.5873	pathogenic	-0.29	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
R/P	0.8939	likely_pathogenic	0.9362	pathogenic	0.038	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
R/Q	0.0909	likely_benign	0.1163	benign	-0.258	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
R/S	0.3705	ambiguous	0.5039	ambiguous	-0.936	Destabilizing	1.0	D	0.766	deleterious	N	0.509243243	None	None	N
R/T	0.1974	likely_benign	0.2923	benign	-0.552	Destabilizing	1.0	D	0.754	deleterious	N	0.444674476	None	None	N
R/V	0.2863	likely_benign	0.3975	ambiguous	0.038	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
R/W	0.194	likely_benign	0.2807	benign	0.142	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
R/Y	0.2863	likely_benign	0.4244	ambiguous	0.401	Stabilizing	1.0	D	0.799	deleterious	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.