TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26389	79390;79391;79392	chr2:178566967;178566966;178566965	chr2:179431694;179431693;179431692
N2AB	24748	74467;74468;74469	chr2:178566967;178566966;178566965	chr2:179431694;179431693;179431692
N2A	23821	71686;71687;71688	chr2:178566967;178566966;178566965	chr2:179431694;179431693;179431692
N2B	17324	52195;52196;52197	chr2:178566967;178566966;178566965	chr2:179431694;179431693;179431692
Novex-1	17449	52570;52571;52572	chr2:178566967;178566966;178566965	chr2:179431694;179431693;179431692
Novex-2	17516	52771;52772;52773	chr2:178566967;178566966;178566965	chr2:179431694;179431693;179431692
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-80
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3278
• 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	rs760307077	-0.72	0.967	N	0.745	0.496	0.651006993216	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
P/L	rs760307077	-0.72	0.967	N	0.745	0.496	0.651006993216	gnomAD-4.0.0	3.18323E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86566E-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	0.0596	likely_benign	0.0638	benign	-1.583	Destabilizing	0.805	D	0.689	prob.neutral	N	0.463700167	None	None	N
P/C	0.3386	likely_benign	0.3452	ambiguous	-1.305	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
P/D	0.7114	likely_pathogenic	0.7334	pathogenic	-2.286	Highly Destabilizing	0.975	D	0.694	prob.neutral	None	None	None	None	N
P/E	0.333	likely_benign	0.3584	ambiguous	-2.286	Highly Destabilizing	0.916	D	0.701	prob.neutral	None	None	None	None	N
P/F	0.4553	ambiguous	0.4402	ambiguous	-1.298	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
P/G	0.3421	ambiguous	0.3659	ambiguous	-1.884	Destabilizing	0.916	D	0.739	prob.delet.	None	None	None	None	N
P/H	0.2486	likely_benign	0.2665	benign	-1.418	Destabilizing	0.997	D	0.759	deleterious	None	None	None	None	N
P/I	0.2932	likely_benign	0.2908	benign	-0.839	Destabilizing	0.987	D	0.788	deleterious	None	None	None	None	N
P/K	0.3102	likely_benign	0.3178	benign	-1.299	Destabilizing	0.845	D	0.696	prob.neutral	None	None	None	None	N
P/L	0.1581	likely_benign	0.1604	benign	-0.839	Destabilizing	0.967	D	0.745	deleterious	N	0.516570651	None	None	N
P/M	0.2697	likely_benign	0.2629	benign	-0.734	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
P/N	0.4525	ambiguous	0.4733	ambiguous	-1.223	Destabilizing	0.975	D	0.735	prob.delet.	None	None	None	None	N
P/Q	0.1512	likely_benign	0.1578	benign	-1.461	Destabilizing	0.967	D	0.689	prob.neutral	N	0.51183371	None	None	N
P/R	0.2057	likely_benign	0.2157	benign	-0.773	Destabilizing	0.056	N	0.633	neutral	N	0.496211444	None	None	N
P/S	0.1214	likely_benign	0.1369	benign	-1.633	Destabilizing	0.426	N	0.507	neutral	N	0.473725869	None	None	N
P/T	0.1344	likely_benign	0.1542	benign	-1.537	Destabilizing	0.805	D	0.71	prob.delet.	N	0.501744852	None	None	N
P/V	0.1928	likely_benign	0.2003	benign	-1.056	Destabilizing	0.987	D	0.727	prob.delet.	None	None	None	None	N
P/W	0.7121	likely_pathogenic	0.7111	pathogenic	-1.507	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
P/Y	0.5181	ambiguous	0.5079	ambiguous	-1.211	Destabilizing	0.999	D	0.793	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.