TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19278	58057;58058;58059	chr2:178595522;178595521;178595520	chr2:179460249;179460248;179460247
N2AB	17637	53134;53135;53136	chr2:178595522;178595521;178595520	chr2:179460249;179460248;179460247
N2A	16710	50353;50354;50355	chr2:178595522;178595521;178595520	chr2:179460249;179460248;179460247
N2B	10213	30862;30863;30864	chr2:178595522;178595521;178595520	chr2:179460249;179460248;179460247
Novex-1	10338	31237;31238;31239	chr2:178595522;178595521;178595520	chr2:179460249;179460248;179460247
Novex-2	10405	31438;31439;31440	chr2:178595522;178595521;178595520	chr2:179460249;179460248;179460247
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-27
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0519
• 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
I/V	rs56025724	-2.308	0.985	N	0.398	0.182	0.602907052046	gnomAD-2.1.1	4.75E-05	None	None	None	None	N	None	0	0	None	0	6.71366E-04	None	0	None	0	0	0
I/V	rs56025724	-2.308	0.985	N	0.398	0.182	0.602907052046	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.9425E-04	None	0	0	0	0	0
I/V	rs56025724	-2.308	0.985	N	0.398	0.182	0.602907052046	gnomAD-4.0.0	7.70423E-06	None	None	None	None	N	None	0	0	None	0	2.63878E-04	None	0	0	8.69667E-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
I/A	0.74	likely_pathogenic	0.7584	pathogenic	-2.978	Highly Destabilizing	0.998	D	0.689	prob.delet.	None	None	None	None	N
I/C	0.8803	likely_pathogenic	0.8853	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
I/D	0.9908	likely_pathogenic	0.9946	pathogenic	-3.496	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
I/E	0.9829	likely_pathogenic	0.9885	pathogenic	-3.293	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
I/F	0.4722	ambiguous	0.5535	ambiguous	-1.71	Destabilizing	0.999	D	0.749	deleterious	D	0.523202336	None	None	N
I/G	0.9636	likely_pathogenic	0.9739	pathogenic	-3.476	Highly Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
I/H	0.9739	likely_pathogenic	0.9839	pathogenic	-2.662	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
I/K	0.968	likely_pathogenic	0.9807	pathogenic	-2.3	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
I/L	0.2697	likely_benign	0.2932	benign	-1.526	Destabilizing	0.985	D	0.422	neutral	N	0.491319204	None	None	N
I/M	0.221	likely_benign	0.2331	benign	-1.705	Destabilizing	0.999	D	0.732	deleterious	N	0.486628247	None	None	N
I/N	0.8739	likely_pathogenic	0.912	pathogenic	-2.657	Highly Destabilizing	0.999	D	0.821	deleterious	D	0.524935919	None	None	N
I/P	0.8799	likely_pathogenic	0.9126	pathogenic	-1.995	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
I/Q	0.9543	likely_pathogenic	0.9687	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
I/R	0.9453	likely_pathogenic	0.9669	pathogenic	-1.864	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
I/S	0.8149	likely_pathogenic	0.8532	pathogenic	-3.318	Highly Destabilizing	0.999	D	0.812	deleterious	D	0.524415844	None	None	N
I/T	0.8005	likely_pathogenic	0.8275	pathogenic	-2.983	Highly Destabilizing	0.999	D	0.822	deleterious	N	0.503827141	None	None	N
I/V	0.1587	likely_benign	0.1535	benign	-1.995	Destabilizing	0.985	D	0.398	neutral	N	0.46963721	None	None	N
I/W	0.976	likely_pathogenic	0.9846	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
I/Y	0.9353	likely_pathogenic	0.957	pathogenic	-1.865	Destabilizing	0.999	D	0.809	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.