TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3117	9574;9575;9576	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606
N2AB	3117	9574;9575;9576	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606
N2A	3117	9574;9575;9576	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606
N2B	3071	9436;9437;9438	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606
Novex-1	3071	9436;9437;9438	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606
Novex-2	3071	9436;9437;9438	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606
Novex-3	3117	9574;9575;9576	chr2:178767881;178767880;178767879	chr2:179632608;179632607;179632606

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-21
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.2633
• 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	rs752062913	None	0.379	N	0.473	0.298	0.577897453458	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs752062913	None	0.379	N	0.473	0.298	0.577897453458	gnomAD-4.0.0	1.85874E-06	None	None	None	None	N	None	1.33472E-05	0	None	0	0	None	0	0	1.69489E-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
P/A	0.1528	likely_benign	0.2045	benign	-1.446	Destabilizing	0.004	N	0.149	neutral	N	0.494848809	None	None	N
P/C	0.8291	likely_pathogenic	0.8681	pathogenic	-1.147	Destabilizing	0.992	D	0.542	neutral	None	None	None	None	N
P/D	0.7832	likely_pathogenic	0.855	pathogenic	-1.052	Destabilizing	0.617	D	0.388	neutral	None	None	None	None	N
P/E	0.6309	likely_pathogenic	0.7118	pathogenic	-1.051	Destabilizing	0.447	N	0.388	neutral	None	None	None	None	N
P/F	0.7365	likely_pathogenic	0.8091	pathogenic	-1.093	Destabilizing	0.92	D	0.568	neutral	None	None	None	None	N
P/G	0.5114	ambiguous	0.5985	pathogenic	-1.767	Destabilizing	0.447	N	0.416	neutral	None	None	None	None	N
P/H	0.4114	ambiguous	0.4956	ambiguous	-1.228	Destabilizing	0.977	D	0.5	neutral	None	None	None	None	N
P/I	0.5643	likely_pathogenic	0.6687	pathogenic	-0.672	Destabilizing	0.739	D	0.538	neutral	None	None	None	None	N
P/K	0.7252	likely_pathogenic	0.7984	pathogenic	-1.175	Destabilizing	0.447	N	0.381	neutral	None	None	None	None	N
P/L	0.2376	likely_benign	0.3023	benign	-0.672	Destabilizing	0.379	N	0.473	neutral	N	0.470106427	None	None	N
P/M	0.554	ambiguous	0.6535	pathogenic	-0.61	Destabilizing	0.92	D	0.504	neutral	None	None	None	None	N
P/N	0.5255	ambiguous	0.6257	pathogenic	-0.976	Destabilizing	0.85	D	0.471	neutral	None	None	None	None	N
P/Q	0.3366	likely_benign	0.4199	ambiguous	-1.14	Destabilizing	0.045	N	0.161	neutral	N	0.440821912	None	None	N
P/R	0.5465	ambiguous	0.5995	pathogenic	-0.673	Destabilizing	0.81	D	0.462	neutral	N	0.473549801	None	None	N
P/S	0.2003	likely_benign	0.2672	benign	-1.561	Destabilizing	0.201	N	0.389	neutral	N	0.424711226	None	None	N
P/T	0.1804	likely_benign	0.2388	benign	-1.444	Destabilizing	0.004	N	0.195	neutral	N	0.482672908	None	None	N
P/V	0.4104	ambiguous	0.514	ambiguous	-0.895	Destabilizing	0.447	N	0.427	neutral	None	None	None	None	N
P/W	0.8804	likely_pathogenic	0.9045	pathogenic	-1.234	Destabilizing	0.992	D	0.597	neutral	None	None	None	None	N
P/Y	0.7097	likely_pathogenic	0.7793	pathogenic	-0.95	Destabilizing	0.92	D	0.583	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.