TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6661	20206;20207;20208	chr2:178727597;178727596;178727595	chr2:179592324;179592323;179592322
N2AB	6344	19255;19256;19257	chr2:178727597;178727596;178727595	chr2:179592324;179592323;179592322
N2A	5417	16474;16475;16476	chr2:178727597;178727596;178727595	chr2:179592324;179592323;179592322
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-50
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0831
• 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/S	rs772138264	-3.619	1.0	D	0.889	0.705	0.858812690212	gnomAD-2.1.1	9.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	8.51E-05	None	0	0	0
L/S	rs772138264	-3.619	1.0	D	0.889	0.705	0.858812690212	gnomAD-4.0.0	8.51844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.46726E-05	3.19857E-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
L/A	0.9122	likely_pathogenic	0.8989	pathogenic	-3.035	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/C	0.9414	likely_pathogenic	0.9267	pathogenic	-2.309	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.9978	pathogenic	-3.659	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.9885	likely_pathogenic	0.9873	pathogenic	-3.348	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/F	0.6747	likely_pathogenic	0.6594	pathogenic	-1.837	Destabilizing	0.907	D	0.438	neutral	N	0.516844729	None	None	N
L/G	0.9796	likely_pathogenic	0.9766	pathogenic	-3.659	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/H	0.9711	likely_pathogenic	0.9711	pathogenic	-3.19	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/I	0.2587	likely_benign	0.2218	benign	-1.167	Destabilizing	0.992	D	0.572	neutral	None	None	None	None	N
L/K	0.9858	likely_pathogenic	0.9859	pathogenic	-2.463	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/M	0.4213	ambiguous	0.4049	ambiguous	-1.22	Destabilizing	1.0	D	0.803	deleterious	D	0.531176776	None	None	N
L/N	0.9878	likely_pathogenic	0.9871	pathogenic	-3.101	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/P	0.9889	likely_pathogenic	0.9865	pathogenic	-1.778	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/Q	0.9532	likely_pathogenic	0.9544	pathogenic	-2.807	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/R	0.9618	likely_pathogenic	0.9637	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/S	0.984	likely_pathogenic	0.9816	pathogenic	-3.757	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.550041499	None	None	N
L/T	0.949	likely_pathogenic	0.939	pathogenic	-3.28	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/V	0.2683	likely_benign	0.2248	benign	-1.778	Destabilizing	0.992	D	0.573	neutral	N	0.488235726	None	None	N
L/W	0.9476	likely_pathogenic	0.9491	pathogenic	-2.274	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.550041499	None	None	N
L/Y	0.9455	likely_pathogenic	0.9484	pathogenic	-2.048	Highly Destabilizing	0.997	D	0.863	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.