TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20831	62716;62717;62718	chr2:178589234;178589233;178589232	chr2:179453961;179453960;179453959
N2AB	19190	57793;57794;57795	chr2:178589234;178589233;178589232	chr2:179453961;179453960;179453959
N2A	18263	55012;55013;55014	chr2:178589234;178589233;178589232	chr2:179453961;179453960;179453959
N2B	11766	35521;35522;35523	chr2:178589234;178589233;178589232	chr2:179453961;179453960;179453959
Novex-1	11891	35896;35897;35898	chr2:178589234;178589233;178589232	chr2:179453961;179453960;179453959
Novex-2	11958	36097;36098;36099	chr2:178589234;178589233;178589232	chr2:179453961;179453960;179453959
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-122
• Domain position: 63
• Structural Position: 140
• Q(SASA): 0.1762
• 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
L/R	None	None	1.0	N	0.893	0.622	0.71338130811	gnomAD-4.0.0	1.59183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-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
L/A	0.6631	likely_pathogenic	0.7412	pathogenic	-2.548	Highly Destabilizing	0.997	D	0.749	deleterious	None	None	None	None	N
L/C	0.5922	likely_pathogenic	0.7111	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/D	0.9914	likely_pathogenic	0.9944	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/E	0.9476	likely_pathogenic	0.9604	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/F	0.3082	likely_benign	0.365	ambiguous	-1.71	Destabilizing	0.999	D	0.807	deleterious	N	0.487327254	None	None	N
L/G	0.9385	likely_pathogenic	0.9632	pathogenic	-3.02	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/H	0.7886	likely_pathogenic	0.8497	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.877	deleterious	N	0.501460542	None	None	N
L/I	0.1078	likely_benign	0.1078	benign	-1.225	Destabilizing	0.992	D	0.639	neutral	N	0.315032724	None	None	N
L/K	0.8759	likely_pathogenic	0.8974	pathogenic	-1.884	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/M	0.1294	likely_benign	0.1432	benign	-1.234	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/N	0.9277	likely_pathogenic	0.957	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/P	0.9886	likely_pathogenic	0.9923	pathogenic	-1.643	Destabilizing	1.0	D	0.893	deleterious	N	0.501460542	None	None	N
L/Q	0.688	likely_pathogenic	0.746	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/R	0.8256	likely_pathogenic	0.862	pathogenic	-1.409	Destabilizing	1.0	D	0.893	deleterious	N	0.501460542	None	None	N
L/S	0.8559	likely_pathogenic	0.9069	pathogenic	-2.813	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/T	0.7508	likely_pathogenic	0.8171	pathogenic	-2.528	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/V	0.1114	likely_benign	0.1137	benign	-1.643	Destabilizing	0.767	D	0.391	neutral	N	0.442418897	None	None	N
L/W	0.7194	likely_pathogenic	0.7942	pathogenic	-1.891	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/Y	0.7092	likely_pathogenic	0.7925	pathogenic	-1.656	Destabilizing	1.0	D	0.827	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.