TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30467	91624;91625;91626	chr2:178551132;178551131;178551130	chr2:179415859;179415858;179415857
N2AB	28826	86701;86702;86703	chr2:178551132;178551131;178551130	chr2:179415859;179415858;179415857
N2A	27899	83920;83921;83922	chr2:178551132;178551131;178551130	chr2:179415859;179415858;179415857
N2B	21402	64429;64430;64431	chr2:178551132;178551131;178551130	chr2:179415859;179415858;179415857
Novex-1	21527	64804;64805;64806	chr2:178551132;178551131;178551130	chr2:179415859;179415858;179415857
Novex-2	21594	65005;65006;65007	chr2:178551132;178551131;178551130	chr2:179415859;179415858;179415857
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: Fn3-110
• Domain position: 46
• Structural Position: 64
• Q(SASA): 0.8842
• 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/C	rs775591945	-0.078	1.0	N	0.551	0.288	None	gnomAD-2.1.1	5.72E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	1.0179E-04	1.40845E-04
R/C	rs775591945	-0.078	1.0	N	0.551	0.288	None	gnomAD-3.1.2	1.05255E-04	None	None	None	None	N	None	9.67E-05	0	0	0	1.92976E-04	None	0	0	1.61731E-04	0	0
R/C	rs775591945	-0.078	1.0	N	0.551	0.288	None	gnomAD-4.0.0	1.76042E-04	None	None	None	None	N	None	6.68271E-05	5.004E-05	None	0	8.93017E-05	None	0	0	2.23796E-04	3.29424E-05	8.00717E-05
R/H	rs572793448	-0.555	0.26	N	0.301	0.145	None	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	2.06817E-04	0	None	0	0	None	0	None	0	7.83E-06	0
R/H	rs572793448	-0.555	0.26	N	0.301	0.145	None	gnomAD-3.1.2	8.54E-05	None	None	None	None	N	None	3.13813E-04	0	0	0	0	None	0	0	0	0	0
R/H	rs572793448	-0.555	0.26	N	0.301	0.145	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/H	rs572793448	-0.555	0.26	N	0.301	0.145	None	gnomAD-4.0.0	1.36348E-05	None	None	None	None	N	None	2.13333E-04	0	None	0	8.93136E-05	None	0	0	8.47693E-07	0	1.60097E-05
R/S	None	None	0.956	N	0.523	0.229	0.341934017632	gnomAD-4.0.0	6.84349E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99575E-07	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	0.5898	likely_pathogenic	0.6488	pathogenic	0.118	Stabilizing	0.919	D	0.5	neutral	None	None	None	None	N
R/C	0.3805	ambiguous	0.4064	ambiguous	-0.176	Destabilizing	1.0	D	0.551	neutral	N	0.482142432	None	None	N
R/D	0.7509	likely_pathogenic	0.8047	pathogenic	-0.284	Destabilizing	0.976	D	0.481	neutral	None	None	None	None	N
R/E	0.5487	ambiguous	0.6098	pathogenic	-0.232	Destabilizing	0.919	D	0.497	neutral	None	None	None	None	N
R/F	0.7542	likely_pathogenic	0.7952	pathogenic	-0.159	Destabilizing	0.988	D	0.53	neutral	None	None	None	None	N
R/G	0.3958	ambiguous	0.4585	ambiguous	-0.04	Destabilizing	0.956	D	0.512	neutral	N	0.456446121	None	None	N
R/H	0.1637	likely_benign	0.1738	benign	-0.563	Destabilizing	0.26	N	0.301	neutral	N	0.495719372	None	None	N
R/I	0.4983	ambiguous	0.5361	ambiguous	0.491	Stabilizing	0.988	D	0.525	neutral	None	None	None	None	N
R/K	0.1134	likely_benign	0.1242	benign	-0.086	Destabilizing	0.06	N	0.213	neutral	None	None	None	None	N
R/L	0.4254	ambiguous	0.4649	ambiguous	0.491	Stabilizing	0.956	D	0.489	neutral	N	0.47626682	None	None	N
R/M	0.4816	ambiguous	0.524	ambiguous	-0.022	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
R/N	0.679	likely_pathogenic	0.7248	pathogenic	-0.004	Destabilizing	0.919	D	0.493	neutral	None	None	None	None	N
R/P	0.587	likely_pathogenic	0.6568	pathogenic	0.386	Stabilizing	0.998	D	0.525	neutral	N	0.488579969	None	None	N
R/Q	0.1654	likely_benign	0.1732	benign	-0.028	Destabilizing	0.919	D	0.513	neutral	None	None	None	None	N
R/S	0.6932	likely_pathogenic	0.7429	pathogenic	-0.167	Destabilizing	0.956	D	0.523	neutral	N	0.463452238	None	None	N
R/T	0.4637	ambiguous	0.5225	ambiguous	-0.002	Destabilizing	0.959	D	0.503	neutral	None	None	None	None	N
R/V	0.553	ambiguous	0.603	pathogenic	0.386	Stabilizing	0.988	D	0.537	neutral	None	None	None	None	N
R/W	0.364	ambiguous	0.4059	ambiguous	-0.336	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
R/Y	0.533	ambiguous	0.584	pathogenic	0.076	Stabilizing	0.976	D	0.517	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.