TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19043	57352;57353;57354	chr2:178598043;178598042;178598041	chr2:179462770;179462769;179462768
N2AB	17402	52429;52430;52431	chr2:178598043;178598042;178598041	chr2:179462770;179462769;179462768
N2A	16475	49648;49649;49650	chr2:178598043;178598042;178598041	chr2:179462770;179462769;179462768
N2B	9978	30157;30158;30159	chr2:178598043;178598042;178598041	chr2:179462770;179462769;179462768
Novex-1	10103	30532;30533;30534	chr2:178598043;178598042;178598041	chr2:179462770;179462769;179462768
Novex-2	10170	30733;30734;30735	chr2:178598043;178598042;178598041	chr2:179462770;179462769;179462768
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-26
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1447
• 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
V/A	rs567967628	-1.838	0.78	N	0.547	0.234	0.422883881359	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.31216E-04	None	0	0	0
V/A	rs567967628	-1.838	0.78	N	0.547	0.234	0.422883881359	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
V/A	rs567967628	-1.838	0.78	N	0.547	0.234	0.422883881359	gnomAD-4.0.0	4.96129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.79624E-05	0
V/E	None	None	0.995	N	0.756	0.459	0.746793126172	gnomAD-4.0.0	6.84701E-07	None	None	None	None	N	None	0	0	None	0	2.52181E-05	None	0	0	0	0	0
V/G	rs567967628	-2.545	0.995	N	0.779	0.424	0.785639203354	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.84E-05	None	0	0	0
V/G	rs567967628	-2.545	0.995	N	0.779	0.424	0.785639203354	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
V/G	rs567967628	-2.545	0.995	N	0.779	0.424	0.785639203354	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
V/G	rs567967628	-2.545	0.995	N	0.779	0.424	0.785639203354	gnomAD-4.0.0	5.58104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.79662E-05	1.60154E-05
V/M	rs1406392460	None	0.968	N	0.667	0.265	0.351614576976	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	0	None	0	0	0	0	0
V/M	rs1406392460	None	0.968	N	0.667	0.265	0.351614576976	gnomAD-4.0.0	3.0451E-06	None	None	None	None	N	None	3.49455E-05	6.1546E-05	None	0	0	None	0	0	0	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
V/A	0.4557	ambiguous	0.4742	ambiguous	-1.662	Destabilizing	0.78	D	0.547	neutral	N	0.468036913	None	None	N
V/C	0.7985	likely_pathogenic	0.7743	pathogenic	-1.053	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
V/D	0.8592	likely_pathogenic	0.8568	pathogenic	-1.841	Destabilizing	0.996	D	0.809	deleterious	None	None	None	None	N
V/E	0.7149	likely_pathogenic	0.7231	pathogenic	-1.664	Destabilizing	0.995	D	0.756	deleterious	N	0.510019608	None	None	N
V/F	0.3387	likely_benign	0.3368	benign	-0.957	Destabilizing	0.976	D	0.719	prob.delet.	None	None	None	None	N
V/G	0.5004	ambiguous	0.5076	ambiguous	-2.156	Highly Destabilizing	0.995	D	0.779	deleterious	N	0.474522955	None	None	N
V/H	0.8899	likely_pathogenic	0.8929	pathogenic	-1.847	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/I	0.0774	likely_benign	0.0767	benign	-0.318	Destabilizing	0.015	N	0.242	neutral	None	None	None	None	N
V/K	0.8357	likely_pathogenic	0.8505	pathogenic	-1.32	Destabilizing	0.988	D	0.76	deleterious	None	None	None	None	N
V/L	0.3036	likely_benign	0.284	benign	-0.318	Destabilizing	0.437	N	0.413	neutral	N	0.454336897	None	None	N
V/M	0.2661	likely_benign	0.2723	benign	-0.297	Destabilizing	0.968	D	0.667	neutral	N	0.504325787	None	None	N
V/N	0.6739	likely_pathogenic	0.6914	pathogenic	-1.48	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
V/P	0.9293	likely_pathogenic	0.9214	pathogenic	-0.736	Destabilizing	0.996	D	0.734	prob.delet.	None	None	None	None	N
V/Q	0.707	likely_pathogenic	0.7274	pathogenic	-1.382	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
V/R	0.8095	likely_pathogenic	0.8239	pathogenic	-1.141	Destabilizing	0.996	D	0.804	deleterious	None	None	None	None	N
V/S	0.6006	likely_pathogenic	0.6111	pathogenic	-2.104	Highly Destabilizing	0.988	D	0.721	prob.delet.	None	None	None	None	N
V/T	0.4651	ambiguous	0.4911	ambiguous	-1.785	Destabilizing	0.919	D	0.619	neutral	None	None	None	None	N
V/W	0.9172	likely_pathogenic	0.9186	pathogenic	-1.41	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
V/Y	0.7674	likely_pathogenic	0.7642	pathogenic	-0.985	Destabilizing	0.996	D	0.726	prob.delet.	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.