TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28599	86020;86021;86022	chr2:178560337;178560336;178560335	chr2:179425064;179425063;179425062
N2AB	26958	81097;81098;81099	chr2:178560337;178560336;178560335	chr2:179425064;179425063;179425062
N2A	26031	78316;78317;78318	chr2:178560337;178560336;178560335	chr2:179425064;179425063;179425062
N2B	19534	58825;58826;58827	chr2:178560337;178560336;178560335	chr2:179425064;179425063;179425062
Novex-1	19659	59200;59201;59202	chr2:178560337;178560336;178560335	chr2:179425064;179425063;179425062
Novex-2	19726	59401;59402;59403	chr2:178560337;178560336;178560335	chr2:179425064;179425063;179425062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-96
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4265
• 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
R/C	rs755081931	-0.522	1.0	N	0.764	0.495	0.717669958738	gnomAD-2.1.1	7.14E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	2.81452E-04
R/C	rs755081931	-0.522	1.0	N	0.764	0.495	0.717669958738	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.45E-05	0	0	0	0
R/C	rs755081931	-0.522	1.0	N	0.764	0.495	0.717669958738	gnomAD-4.0.0	8.67683E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.56353E-05	1.64528E-04	7.62864E-06	3.29453E-05	0
R/H	rs558543425	-1.355	1.0	N	0.762	0.376	0.307016933798	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	4.14E-05	0	None	0	0	None	6.54E-05	None	0	1.56E-05	0
R/H	rs558543425	-1.355	1.0	N	0.762	0.376	0.307016933798	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	2.07297E-04	0
R/H	rs558543425	-1.355	1.0	N	0.762	0.376	0.307016933798	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/H	rs558543425	-1.355	1.0	N	0.762	0.376	0.307016933798	gnomAD-4.0.0	1.98299E-05	None	None	None	None	I	None	1.33294E-05	0	None	0	2.23025E-05	None	0	0	2.28859E-05	3.29402E-05	0
R/P	rs558543425	-0.319	1.0	N	0.769	0.436	0.494769474416	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/P	rs558543425	-0.319	1.0	N	0.769	0.436	0.494769474416	gnomAD-4.0.0	2.05268E-06	None	None	None	None	I	None	2.98793E-05	0	None	0	0	None	0	0	1.79894E-06	0	0
R/S	rs755081931	-0.879	1.0	N	0.772	0.467	0.430808444494	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
R/S	rs755081931	-0.879	1.0	N	0.772	0.467	0.430808444494	gnomAD-4.0.0	4.78968E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29635E-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
R/A	0.6915	likely_pathogenic	0.6987	pathogenic	-0.592	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	I
R/C	0.2752	likely_benign	0.2734	benign	-0.653	Destabilizing	1.0	D	0.764	deleterious	N	0.497817605	None	None	I
R/D	0.9391	likely_pathogenic	0.9436	pathogenic	0.062	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
R/E	0.7395	likely_pathogenic	0.7545	pathogenic	0.201	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
R/F	0.8315	likely_pathogenic	0.8345	pathogenic	-0.344	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
R/G	0.6343	likely_pathogenic	0.6573	pathogenic	-0.914	Destabilizing	1.0	D	0.715	prob.delet.	N	0.467596576	None	None	I
R/H	0.2107	likely_benign	0.2137	benign	-1.179	Destabilizing	1.0	D	0.762	deleterious	N	0.466542938	None	None	I
R/I	0.5847	likely_pathogenic	0.5859	pathogenic	0.271	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
R/K	0.1558	likely_benign	0.1536	benign	-0.624	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	I
R/L	0.4694	ambiguous	0.4707	ambiguous	0.271	Stabilizing	1.0	D	0.715	prob.delet.	N	0.508976671	None	None	I
R/M	0.5227	ambiguous	0.5312	ambiguous	-0.222	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
R/N	0.8781	likely_pathogenic	0.8824	pathogenic	-0.23	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
R/P	0.5787	likely_pathogenic	0.5613	ambiguous	0.005	Stabilizing	1.0	D	0.769	deleterious	N	0.453238032	None	None	I
R/Q	0.195	likely_benign	0.196	benign	-0.309	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/S	0.8476	likely_pathogenic	0.8513	pathogenic	-0.931	Destabilizing	1.0	D	0.772	deleterious	N	0.501951911	None	None	I
R/T	0.5966	likely_pathogenic	0.6023	pathogenic	-0.604	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
R/V	0.6445	likely_pathogenic	0.6352	pathogenic	0.005	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
R/W	0.313	likely_benign	0.331	benign	-0.038	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/Y	0.6641	likely_pathogenic	0.6768	pathogenic	0.255	Stabilizing	1.0	D	0.775	deleterious	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.