TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31020	93283;93284;93285	chr2:178548568;178548567;178548566	chr2:179413295;179413294;179413293
N2AB	29379	88360;88361;88362	chr2:178548568;178548567;178548566	chr2:179413295;179413294;179413293
N2A	28452	85579;85580;85581	chr2:178548568;178548567;178548566	chr2:179413295;179413294;179413293
N2B	21955	66088;66089;66090	chr2:178548568;178548567;178548566	chr2:179413295;179413294;179413293
Novex-1	22080	66463;66464;66465	chr2:178548568;178548567;178548566	chr2:179413295;179413294;179413293
Novex-2	22147	66664;66665;66666	chr2:178548568;178548567;178548566	chr2:179413295;179413294;179413293
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-114
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0866
• 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
P/L	rs1312330710	-0.48	1.0	D	0.938	0.712	0.903324448379	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/L	rs1312330710	-0.48	1.0	D	0.938	0.712	0.903324448379	gnomAD-4.0.0	3.18221E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71608E-06	0	0
P/R	rs1312330710	-1.698	1.0	D	0.961	0.759	0.813260256209	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/R	rs1312330710	-1.698	1.0	D	0.961	0.759	0.813260256209	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.4108E-04	0	0	0
P/S	rs944645264	-2.858	1.0	D	0.907	0.806	0.752574999803	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.9E-06	0
P/S	rs944645264	-2.858	1.0	D	0.907	0.806	0.752574999803	gnomAD-4.0.0	1.09469E-05	None	None	None	None	N	None	5.97586E-05	0	None	0	0	None	0	0	1.25923E-05	0	0
P/T	rs944645264	-2.426	1.0	D	0.902	0.765	0.748360532628	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/T	rs944645264	-2.426	1.0	D	0.902	0.765	0.748360532628	gnomAD-4.0.0	3.4209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99449E-07	4.63725E-05	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
P/A	0.223	likely_benign	0.2233	benign	-2.229	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.605334952	None	None	N
P/C	0.6388	likely_pathogenic	0.6325	pathogenic	-1.836	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
P/D	0.997	likely_pathogenic	0.9961	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/E	0.9886	likely_pathogenic	0.9873	pathogenic	-2.853	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/F	0.9927	likely_pathogenic	0.9917	pathogenic	-1.214	Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
P/G	0.9297	likely_pathogenic	0.9172	pathogenic	-2.778	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
P/H	0.9846	likely_pathogenic	0.9795	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.914	deleterious	D	0.663517199	None	None	N
P/I	0.6078	likely_pathogenic	0.6128	pathogenic	-0.674	Destabilizing	1.0	D	0.955	deleterious	None	None	None	None	N
P/K	0.9953	likely_pathogenic	0.9937	pathogenic	-1.825	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/L	0.6458	likely_pathogenic	0.6347	pathogenic	-0.674	Destabilizing	1.0	D	0.938	deleterious	D	0.647094229	None	None	N
P/M	0.8753	likely_pathogenic	0.8652	pathogenic	-0.91	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/N	0.989	likely_pathogenic	0.9855	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.961	deleterious	None	None	None	None	N
P/Q	0.9701	likely_pathogenic	0.9653	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
P/R	0.9827	likely_pathogenic	0.9779	pathogenic	-1.716	Destabilizing	1.0	D	0.961	deleterious	D	0.631044508	None	None	N
P/S	0.7024	likely_pathogenic	0.6843	pathogenic	-2.806	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.630842704	None	None	N
P/T	0.4521	ambiguous	0.4222	ambiguous	-2.421	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.589487035	None	None	N
P/V	0.3098	likely_benign	0.2998	benign	-1.169	Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
P/W	0.9985	likely_pathogenic	0.9984	pathogenic	-1.795	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
P/Y	0.997	likely_pathogenic	0.9961	pathogenic	-1.441	Destabilizing	1.0	D	0.953	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.