TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27396	82411;82412;82413	chr2:178563946;178563945;178563944	chr2:179428673;179428672;179428671
N2AB	25755	77488;77489;77490	chr2:178563946;178563945;178563944	chr2:179428673;179428672;179428671
N2A	24828	74707;74708;74709	chr2:178563946;178563945;178563944	chr2:179428673;179428672;179428671
N2B	18331	55216;55217;55218	chr2:178563946;178563945;178563944	chr2:179428673;179428672;179428671
Novex-1	18456	55591;55592;55593	chr2:178563946;178563945;178563944	chr2:179428673;179428672;179428671
Novex-2	18523	55792;55793;55794	chr2:178563946;178563945;178563944	chr2:179428673;179428672;179428671
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-87
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.4934
• 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
Q/E	rs371604558	0.287	0.285	N	0.363	0.316	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	6.46E-05	1.16003E-04	None	0	0	None	0	None	0	1.78E-05	0
Q/E	rs371604558	0.287	0.285	N	0.363	0.316	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	I	None	4.83E-05	3.93443E-04	0	0	0	None	0	0	4.41E-05	0	0
Q/E	rs371604558	0.287	0.285	N	0.363	0.316	None	gnomAD-4.0.0	2.1072E-05	None	None	None	None	I	None	2.67101E-05	1.66761E-04	None	0	0	None	0	0	1.69533E-05	0	3.20225E-05
Q/L	rs367804525	0.318	0.326	N	0.438	0.201	None	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	6.46E-05	1.15982E-04	None	0	0	None	0	None	0	1.78E-05	0
Q/L	rs367804525	0.318	0.326	N	0.438	0.201	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	I	None	4.83E-05	3.93185E-04	0	0	0	None	0	0	4.41E-05	0	0
Q/L	rs367804525	0.318	0.326	N	0.438	0.201	None	gnomAD-4.0.0	2.10706E-05	None	None	None	None	I	None	2.6698E-05	1.66728E-04	None	0	0	None	0	0	1.69531E-05	0	3.20225E-05
Q/R	rs367804525	0.436	0.491	N	0.367	0.167	0.202949470691	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/R	rs367804525	0.436	0.491	N	0.367	0.167	0.202949470691	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/R	rs367804525	0.436	0.491	N	0.367	0.167	0.202949470691	gnomAD-4.0.0	1.23945E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47653E-07	1.09784E-05	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
Q/A	0.2504	likely_benign	0.2434	benign	-0.191	Destabilizing	0.345	N	0.38	neutral	None	None	None	None	I
Q/C	0.5593	ambiguous	0.5677	pathogenic	0.189	Stabilizing	0.991	D	0.371	neutral	None	None	None	None	I
Q/D	0.2681	likely_benign	0.2777	benign	0.034	Stabilizing	0.561	D	0.345	neutral	None	None	None	None	I
Q/E	0.0738	likely_benign	0.0782	benign	0.001	Stabilizing	0.285	N	0.363	neutral	N	0.410039041	None	None	I
Q/F	0.6538	likely_pathogenic	0.6469	pathogenic	-0.418	Destabilizing	0.39	N	0.47	neutral	None	None	None	None	I
Q/G	0.3018	likely_benign	0.3009	benign	-0.37	Destabilizing	0.561	D	0.438	neutral	None	None	None	None	I
Q/H	0.1745	likely_benign	0.1885	benign	-0.302	Destabilizing	None	N	0.071	neutral	N	0.416101009	None	None	I
Q/I	0.5204	ambiguous	0.4986	ambiguous	0.19	Stabilizing	0.818	D	0.439	neutral	None	None	None	None	I
Q/K	0.1508	likely_benign	0.1557	benign	0.079	Stabilizing	0.285	N	0.387	neutral	N	0.467201833	None	None	I
Q/L	0.1517	likely_benign	0.1394	benign	0.19	Stabilizing	0.326	N	0.438	neutral	N	0.477264111	None	None	I
Q/M	0.3955	ambiguous	0.3702	ambiguous	0.42	Stabilizing	0.965	D	0.322	neutral	None	None	None	None	I
Q/N	0.246	likely_benign	0.2477	benign	-0.2	Destabilizing	0.561	D	0.331	neutral	None	None	None	None	I
Q/P	0.4658	ambiguous	0.4636	ambiguous	0.091	Stabilizing	0.954	D	0.398	neutral	N	0.458371706	None	None	I
Q/R	0.1479	likely_benign	0.1523	benign	0.212	Stabilizing	0.491	N	0.367	neutral	N	0.438823153	None	None	I
Q/S	0.2623	likely_benign	0.259	benign	-0.197	Destabilizing	0.345	N	0.326	neutral	None	None	None	None	I
Q/T	0.2864	likely_benign	0.2838	benign	-0.077	Destabilizing	0.722	D	0.411	neutral	None	None	None	None	I
Q/V	0.331	likely_benign	0.3124	benign	0.091	Stabilizing	0.561	D	0.463	neutral	None	None	None	None	I
Q/W	0.5325	ambiguous	0.543	ambiguous	-0.407	Destabilizing	0.972	D	0.364	neutral	None	None	None	None	I
Q/Y	0.4027	ambiguous	0.408	ambiguous	-0.146	Destabilizing	0.004	N	0.141	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.