TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33281	100066;100067;100068	chr2:178537366;178537365;178537364	chr2:179402093;179402092;179402091
N2AB	31640	95143;95144;95145	chr2:178537366;178537365;178537364	chr2:179402093;179402092;179402091
N2A	30713	92362;92363;92364	chr2:178537366;178537365;178537364	chr2:179402093;179402092;179402091
N2B	24216	72871;72872;72873	chr2:178537366;178537365;178537364	chr2:179402093;179402092;179402091
Novex-1	24341	73246;73247;73248	chr2:178537366;178537365;178537364	chr2:179402093;179402092;179402091
Novex-2	24408	73447;73448;73449	chr2:178537366;178537365;178537364	chr2:179402093;179402092;179402091
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-157
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.1569
• 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/T	None	None	None	N	0.191	0.091	0.24896430686	gnomAD-4.0.0	6.97564E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6913E-05

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	0.4659	ambiguous	0.4981	ambiguous	-0.827	Destabilizing	0.946	D	0.485	neutral	None	None	None	None	N
A/D	0.4596	ambiguous	0.4599	ambiguous	-0.746	Destabilizing	0.266	N	0.577	neutral	D	0.538217435	None	None	N
A/E	0.3607	ambiguous	0.3793	ambiguous	-0.823	Destabilizing	0.954	D	0.472	neutral	None	None	None	None	N
A/F	0.4507	ambiguous	0.5059	ambiguous	-0.734	Destabilizing	0.985	D	0.597	neutral	None	None	None	None	N
A/G	0.2264	likely_benign	0.2161	benign	-0.655	Destabilizing	0.014	N	0.371	neutral	N	0.509108036	None	None	N
A/H	0.5347	ambiguous	0.5431	ambiguous	-0.671	Destabilizing	0.99	D	0.573	neutral	None	None	None	None	N
A/I	0.3106	likely_benign	0.3764	ambiguous	-0.203	Destabilizing	0.822	D	0.506	neutral	None	None	None	None	N
A/K	0.4557	ambiguous	0.4629	ambiguous	-1.016	Destabilizing	0.982	D	0.465	neutral	None	None	None	None	N
A/L	0.2807	likely_benign	0.3269	benign	-0.203	Destabilizing	0.656	D	0.453	neutral	None	None	None	None	N
A/M	0.2268	likely_benign	0.2755	benign	-0.36	Destabilizing	0.985	D	0.501	neutral	None	None	None	None	N
A/N	0.3335	likely_benign	0.3715	ambiguous	-0.754	Destabilizing	0.053	N	0.606	neutral	None	None	None	None	N
A/P	0.9599	likely_pathogenic	0.9595	pathogenic	-0.258	Destabilizing	0.42	N	0.511	neutral	D	0.538910868	None	None	N
A/Q	0.406	ambiguous	0.4188	ambiguous	-0.934	Destabilizing	0.926	D	0.519	neutral	None	None	None	None	N
A/R	0.4107	ambiguous	0.4157	ambiguous	-0.587	Destabilizing	0.997	D	0.506	neutral	None	None	None	None	N
A/S	0.118	likely_benign	0.1219	benign	-1.011	Destabilizing	None	N	0.197	neutral	N	0.467701344	None	None	N
A/T	0.0678	likely_benign	0.0795	benign	-0.994	Destabilizing	None	N	0.191	neutral	N	0.448288864	None	None	N
A/V	0.1514	likely_benign	0.1823	benign	-0.258	Destabilizing	0.35	N	0.361	neutral	N	0.478438412	None	None	N
A/W	0.8464	likely_pathogenic	0.8572	pathogenic	-0.999	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
A/Y	0.5582	ambiguous	0.5961	pathogenic	-0.617	Destabilizing	0.985	D	0.595	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.