TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13736	41431;41432;41433	chr2:178636521;178636520;178636519	chr2:179501248;179501247;179501246
N2AB	12095	36508;36509;36510	chr2:178636521;178636520;178636519	chr2:179501248;179501247;179501246
N2A	11168	33727;33728;33729	chr2:178636521;178636520;178636519	chr2:179501248;179501247;179501246
N2B	4671	14236;14237;14238	chr2:178636521;178636520;178636519	chr2:179501248;179501247;179501246
Novex-1	4796	14611;14612;14613	chr2:178636521;178636520;178636519	chr2:179501248;179501247;179501246
Novex-2	4863	14812;14813;14814	chr2:178636521;178636520;178636519	chr2:179501248;179501247;179501246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-87
• Domain position: 53
• Structural Position: 127
• Q(SASA): 0.3594
• 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
A/S	rs540133480	-0.398	0.079	N	0.336	0.092	0.263140351381	gnomAD-2.1.1	6.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	6.39693E-04	2.35E-05	0
A/S	rs540133480	-0.398	0.079	N	0.336	0.092	0.263140351381	gnomAD-3.1.2	7.89E-05	None	None	None	None	N	None	0	0	0	0	0	None	1.03598E-03	0	1.47E-05	0	0
A/S	rs540133480	-0.398	0.079	N	0.336	0.092	0.263140351381	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	2E-03	None	None	None	0	None
A/S	rs540133480	-0.398	0.079	N	0.336	0.092	0.263140351381	gnomAD-4.0.0	4.77231E-05	None	None	None	None	N	None	0	0	None	0	0	None	7.96825E-04	0	2.03462E-05	0	3.20205E-05
A/T	rs540133480	-0.434	0.885	N	0.648	0.137	0.401327265625	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	1.29216E-04	0	None	0	0	None	0	None	0	0	0
A/T	rs540133480	-0.434	0.885	N	0.648	0.137	0.401327265625	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs540133480	-0.434	0.885	N	0.648	0.137	0.401327265625	gnomAD-4.0.0	3.09913E-06	None	None	None	None	N	None	1.33511E-05	0	None	0	0	None	0	0	2.54326E-06	0	1.60159E-05
A/V	rs574135671	-0.144	0.939	N	0.661	0.329	0.455996456696	gnomAD-2.1.1	6.08E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	6.39591E-04	7.83E-06	0
A/V	rs574135671	-0.144	0.939	N	0.661	0.329	0.455996456696	gnomAD-3.1.2	7.89E-05	None	None	None	None	N	None	0	0	0	0	0	None	1.03695E-03	0	1.47E-05	0	0
A/V	rs574135671	-0.144	0.939	N	0.661	0.329	0.455996456696	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	2E-03	None	None	None	0	None
A/V	rs574135671	-0.144	0.939	N	0.661	0.329	0.455996456696	gnomAD-4.0.0	7.1766E-05	None	None	None	None	N	None	0	0	None	0	0	None	8.00452E-04	0	7.18277E-06	1.34009E-05	2.84414E-05

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
A/C	0.8659	likely_pathogenic	0.9024	pathogenic	-0.76	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
A/D	0.9081	likely_pathogenic	0.942	pathogenic	-0.706	Destabilizing	0.986	D	0.707	prob.neutral	None	None	None	None	N
A/E	0.8348	likely_pathogenic	0.8941	pathogenic	-0.864	Destabilizing	0.939	D	0.649	neutral	N	0.490049467	None	None	N
A/F	0.7641	likely_pathogenic	0.84	pathogenic	-1.048	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
A/G	0.3976	ambiguous	0.4898	ambiguous	-0.477	Destabilizing	0.76	D	0.635	neutral	N	0.498510113	None	None	N
A/H	0.8695	likely_pathogenic	0.9162	pathogenic	-0.538	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
A/I	0.7635	likely_pathogenic	0.8251	pathogenic	-0.451	Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
A/K	0.9528	likely_pathogenic	0.9709	pathogenic	-0.746	Destabilizing	0.953	D	0.651	neutral	None	None	None	None	N
A/L	0.5966	likely_pathogenic	0.6867	pathogenic	-0.451	Destabilizing	0.953	D	0.657	neutral	None	None	None	None	N
A/M	0.6686	likely_pathogenic	0.7396	pathogenic	-0.374	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
A/N	0.6987	likely_pathogenic	0.77	pathogenic	-0.396	Destabilizing	0.986	D	0.699	prob.neutral	None	None	None	None	N
A/P	0.8714	likely_pathogenic	0.8975	pathogenic	-0.405	Destabilizing	0.991	D	0.707	prob.neutral	N	0.50170587	None	None	N
A/Q	0.7182	likely_pathogenic	0.7996	pathogenic	-0.717	Destabilizing	0.993	D	0.713	prob.delet.	None	None	None	None	N
A/R	0.9003	likely_pathogenic	0.935	pathogenic	-0.23	Destabilizing	0.986	D	0.709	prob.delet.	None	None	None	None	N
A/S	0.1195	likely_benign	0.1436	benign	-0.579	Destabilizing	0.079	N	0.336	neutral	N	0.407118936	None	None	N
A/T	0.247	likely_benign	0.2996	benign	-0.663	Destabilizing	0.885	D	0.648	neutral	N	0.481438678	None	None	N
A/V	0.4941	ambiguous	0.5878	pathogenic	-0.405	Destabilizing	0.939	D	0.661	neutral	N	0.46947419	None	None	N
A/W	0.9631	likely_pathogenic	0.9794	pathogenic	-1.178	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
A/Y	0.8899	likely_pathogenic	0.9247	pathogenic	-0.836	Destabilizing	0.998	D	0.765	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.