TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32998	99217;99218;99219	chr2:178538837;178538836;178538835	chr2:179403564;179403563;179403562
N2AB	31357	94294;94295;94296	chr2:178538837;178538836;178538835	chr2:179403564;179403563;179403562
N2A	30430	91513;91514;91515	chr2:178538837;178538836;178538835	chr2:179403564;179403563;179403562
N2B	23933	72022;72023;72024	chr2:178538837;178538836;178538835	chr2:179403564;179403563;179403562
Novex-1	24058	72397;72398;72399	chr2:178538837;178538836;178538835	chr2:179403564;179403563;179403562
Novex-2	24125	72598;72599;72600	chr2:178538837;178538836;178538835	chr2:179403564;179403563;179403562
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-129
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6614
• Predicted PPI site: I

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
K/E	rs747243608	0.443	0.997	N	0.643	0.255	0.300449992093	gnomAD-2.1.1	2.95E-05	None	None	None	None	I	None	0	2.14211E-04	None	0	0	None	0	None	0	0	0
K/E	rs747243608	0.443	0.997	N	0.643	0.255	0.300449992093	gnomAD-3.1.2	6.57E-05	None	None	None	None	I	None	0	6.54793E-04	0	0	0	None	0	0	0	0	0
K/E	rs747243608	0.443	0.997	N	0.643	0.255	0.300449992093	gnomAD-4.0.0	2.35186E-05	None	None	None	None	I	None	0	3.16278E-04	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
K/A	0.7745	likely_pathogenic	0.7719	pathogenic	-0.045	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	I
K/C	0.8943	likely_pathogenic	0.8942	pathogenic	-0.49	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
K/D	0.9619	likely_pathogenic	0.9647	pathogenic	-0.259	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
K/E	0.6794	likely_pathogenic	0.6799	pathogenic	-0.279	Destabilizing	0.997	D	0.643	neutral	N	0.466663115	None	None	I
K/F	0.958	likely_pathogenic	0.9587	pathogenic	-0.427	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
K/G	0.9162	likely_pathogenic	0.9178	pathogenic	-0.154	Destabilizing	0.999	D	0.685	prob.delet.	None	None	None	None	I
K/H	0.6921	likely_pathogenic	0.7167	pathogenic	-0.268	Destabilizing	1.0	D	0.669	prob.neutral	None	None	None	None	I
K/I	0.6194	likely_pathogenic	0.6226	pathogenic	0.156	Stabilizing	0.999	D	0.781	deleterious	N	0.485518234	None	None	I
K/L	0.6954	likely_pathogenic	0.7129	pathogenic	0.156	Stabilizing	0.999	D	0.685	prob.delet.	None	None	None	None	I
K/M	0.5659	likely_pathogenic	0.5633	ambiguous	-0.121	Destabilizing	1.0	D	0.661	prob.neutral	None	None	None	None	I
K/N	0.8866	likely_pathogenic	0.8953	pathogenic	-0.023	Destabilizing	0.999	D	0.733	deleterious	N	0.515745141	None	None	I
K/P	0.8685	likely_pathogenic	0.8959	pathogenic	0.111	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
K/Q	0.3886	ambiguous	0.4017	ambiguous	-0.173	Destabilizing	0.999	D	0.749	deleterious	N	0.49715938	None	None	I
K/R	0.1242	likely_benign	0.1314	benign	-0.139	Destabilizing	0.997	D	0.596	neutral	N	0.463604167	None	None	I
K/S	0.8648	likely_pathogenic	0.8718	pathogenic	-0.399	Destabilizing	0.998	D	0.727	deleterious	None	None	None	None	I
K/T	0.5163	ambiguous	0.5359	ambiguous	-0.308	Destabilizing	0.999	D	0.707	prob.delet.	N	0.437206999	None	None	I
K/V	0.5723	likely_pathogenic	0.5883	pathogenic	0.111	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
K/W	0.9729	likely_pathogenic	0.9746	pathogenic	-0.521	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
K/Y	0.9151	likely_pathogenic	0.9163	pathogenic	-0.169	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I

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.