TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15214	45865;45866;45867	chr2:178620970;178620969;178620968	chr2:179485697;179485696;179485695
N2AB	13573	40942;40943;40944	chr2:178620970;178620969;178620968	chr2:179485697;179485696;179485695
N2A	12646	38161;38162;38163	chr2:178620970;178620969;178620968	chr2:179485697;179485696;179485695
N2B	6149	18670;18671;18672	chr2:178620970;178620969;178620968	chr2:179485697;179485696;179485695
Novex-1	6274	19045;19046;19047	chr2:178620970;178620969;178620968	chr2:179485697;179485696;179485695
Novex-2	6341	19246;19247;19248	chr2:178620970;178620969;178620968	chr2:179485697;179485696;179485695
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-104
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2016
• 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
L/P	rs2154211474	None	0.997	N	0.857	0.473	0.720053583897	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.94628E-04	None	0	0	0	0	0
L/P	rs2154211474	None	0.997	N	0.857	0.473	0.720053583897	gnomAD-4.0.0	6.57843E-06	None	None	None	None	I	None	0	0	None	0	1.95084E-04	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
L/A	0.8479	likely_pathogenic	0.8804	pathogenic	-2.21	Highly Destabilizing	0.91	D	0.545	neutral	None	None	None	None	I
L/C	0.9191	likely_pathogenic	0.9237	pathogenic	-1.394	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
L/D	0.9984	likely_pathogenic	0.9987	pathogenic	-2.06	Highly Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	I
L/E	0.986	likely_pathogenic	0.9884	pathogenic	-1.939	Destabilizing	0.993	D	0.843	deleterious	None	None	None	None	I
L/F	0.7654	likely_pathogenic	0.7889	pathogenic	-1.359	Destabilizing	0.991	D	0.693	prob.neutral	D	0.613914355	None	None	I
L/G	0.9827	likely_pathogenic	0.9862	pathogenic	-2.668	Highly Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	I
L/H	0.9838	likely_pathogenic	0.9858	pathogenic	-1.988	Destabilizing	0.999	D	0.85	deleterious	D	0.617217434	None	None	I
L/I	0.1617	likely_benign	0.1749	benign	-0.946	Destabilizing	0.17	N	0.337	neutral	N	0.457821693	None	None	I
L/K	0.984	likely_pathogenic	0.9852	pathogenic	-1.628	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	I
L/M	0.3207	likely_benign	0.3478	ambiguous	-0.761	Destabilizing	0.993	D	0.709	prob.delet.	None	None	None	None	I
L/N	0.9875	likely_pathogenic	0.9904	pathogenic	-1.657	Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	I
L/P	0.7122	likely_pathogenic	0.8226	pathogenic	-1.342	Destabilizing	0.997	D	0.857	deleterious	N	0.467819822	None	None	I
L/Q	0.9468	likely_pathogenic	0.9553	pathogenic	-1.686	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	I
L/R	0.9707	likely_pathogenic	0.9735	pathogenic	-1.164	Destabilizing	0.997	D	0.82	deleterious	D	0.614641559	None	None	I
L/S	0.9722	likely_pathogenic	0.9775	pathogenic	-2.345	Highly Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	I
L/T	0.8933	likely_pathogenic	0.9149	pathogenic	-2.094	Highly Destabilizing	0.986	D	0.723	prob.delet.	None	None	None	None	I
L/V	0.1991	likely_benign	0.2205	benign	-1.342	Destabilizing	0.046	N	0.327	neutral	N	0.508711268	None	None	I
L/W	0.9745	likely_pathogenic	0.9767	pathogenic	-1.621	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	I
L/Y	0.9898	likely_pathogenic	0.9903	pathogenic	-1.359	Destabilizing	0.998	D	0.793	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.