TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5323	16192;16193;16194	chr2:178733326;178733325;178733324	chr2:179598053;179598052;179598051
N2AB	5006	15241;15242;15243	chr2:178733326;178733325;178733324	chr2:179598053;179598052;179598051
N2A	4079	12460;12461;12462	chr2:178733326;178733325;178733324	chr2:179598053;179598052;179598051
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-36
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1262
• 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/G	None	None	0.046	D	0.295	0.458	0.462461958149	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85832E-06	0	0
A/T	rs745667963	-1.293	0.322	N	0.353	0.227	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	1.29199E-04	0	None	0	0	None	0	None	0	0	0
A/T	rs745667963	-1.293	0.322	N	0.353	0.227	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs745667963	-1.293	0.322	N	0.353	0.227	None	gnomAD-4.0.0	3.84332E-06	None	None	None	None	N	None	5.0734E-05	0	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
A/C	0.6701	likely_pathogenic	0.6307	pathogenic	-1.889	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
A/D	0.9824	likely_pathogenic	0.9772	pathogenic	-2.664	Highly Destabilizing	0.982	D	0.645	neutral	D	0.750296045	None	None	N
A/E	0.9649	likely_pathogenic	0.9584	pathogenic	-2.511	Highly Destabilizing	0.986	D	0.661	neutral	None	None	None	None	N
A/F	0.9298	likely_pathogenic	0.9092	pathogenic	-0.944	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	N
A/G	0.473	ambiguous	0.4226	ambiguous	-1.612	Destabilizing	0.046	N	0.295	neutral	D	0.690597404	None	None	N
A/H	0.9828	likely_pathogenic	0.9789	pathogenic	-1.798	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
A/I	0.5254	ambiguous	0.4526	ambiguous	-0.138	Destabilizing	0.986	D	0.663	neutral	None	None	None	None	N
A/K	0.9886	likely_pathogenic	0.9855	pathogenic	-1.291	Destabilizing	0.986	D	0.662	neutral	None	None	None	None	N
A/L	0.5325	ambiguous	0.463	ambiguous	-0.138	Destabilizing	0.91	D	0.619	neutral	None	None	None	None	N
A/M	0.5844	likely_pathogenic	0.5169	ambiguous	-0.644	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
A/N	0.9307	likely_pathogenic	0.9088	pathogenic	-1.628	Destabilizing	0.986	D	0.657	neutral	None	None	None	None	N
A/P	0.7885	likely_pathogenic	0.7921	pathogenic	-0.454	Destabilizing	0.991	D	0.665	neutral	D	0.603794423	None	None	N
A/Q	0.9525	likely_pathogenic	0.9463	pathogenic	-1.55	Destabilizing	0.993	D	0.658	neutral	None	None	None	None	N
A/R	0.9726	likely_pathogenic	0.9669	pathogenic	-1.265	Destabilizing	0.993	D	0.665	neutral	None	None	None	None	N
A/S	0.2184	likely_benign	0.1842	benign	-2.022	Highly Destabilizing	0.885	D	0.454	neutral	D	0.615156598	None	None	N
A/T	0.1736	likely_benign	0.1398	benign	-1.751	Destabilizing	0.322	N	0.353	neutral	N	0.516874392	None	None	N
A/V	0.1843	likely_benign	0.1487	benign	-0.454	Destabilizing	0.885	D	0.553	neutral	N	0.459339332	None	None	N
A/W	0.9914	likely_pathogenic	0.9898	pathogenic	-1.545	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
A/Y	0.9802	likely_pathogenic	0.9754	pathogenic	-1.054	Destabilizing	0.998	D	0.669	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.