TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8988	27187;27188;27189	chr2:178713172;178713171;178713170	chr2:179577899;179577898;179577897
N2AB	8671	26236;26237;26238	chr2:178713172;178713171;178713170	chr2:179577899;179577898;179577897
N2A	7744	23455;23456;23457	chr2:178713172;178713171;178713170	chr2:179577899;179577898;179577897
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-75
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1082
• 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/M	rs2076915849	None	0.971	D	0.573	0.284	0.583928190899	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/M	rs2076915849	None	0.971	D	0.573	0.284	0.583928190899	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4702E-05	0	0
L/P	rs2076915544	None	0.032	N	0.486	0.447	0.714032942311	gnomAD-4.0.0	3.18277E-06	None	None	None	None	N	None	0	0	None	0	5.54754E-05	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	0.536	ambiguous	0.6091	pathogenic	-1.994	Destabilizing	0.754	D	0.461	neutral	None	None	None	None	N
L/C	0.8448	likely_pathogenic	0.8836	pathogenic	-2.58	Highly Destabilizing	0.998	D	0.565	neutral	None	None	None	None	N
L/D	0.992	likely_pathogenic	0.9939	pathogenic	-3.19	Highly Destabilizing	0.956	D	0.673	neutral	None	None	None	None	N
L/E	0.9543	likely_pathogenic	0.9625	pathogenic	-3.116	Highly Destabilizing	0.956	D	0.67	neutral	None	None	None	None	N
L/F	0.7074	likely_pathogenic	0.7766	pathogenic	-1.538	Destabilizing	0.978	D	0.601	neutral	None	None	None	None	N
L/G	0.9128	likely_pathogenic	0.9253	pathogenic	-2.318	Highly Destabilizing	0.956	D	0.666	neutral	None	None	None	None	N
L/H	0.9474	likely_pathogenic	0.9636	pathogenic	-1.497	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
L/I	0.1775	likely_benign	0.2055	benign	-1.118	Destabilizing	0.754	D	0.485	neutral	None	None	None	None	N
L/K	0.956	likely_pathogenic	0.966	pathogenic	-1.801	Destabilizing	0.956	D	0.619	neutral	None	None	None	None	N
L/M	0.2632	likely_benign	0.2926	benign	-1.452	Destabilizing	0.971	D	0.573	neutral	D	0.525421496	None	None	N
L/N	0.948	likely_pathogenic	0.9532	pathogenic	-2.107	Highly Destabilizing	0.978	D	0.683	prob.neutral	None	None	None	None	N
L/P	0.7108	likely_pathogenic	0.7545	pathogenic	-1.388	Destabilizing	0.032	N	0.486	neutral	N	0.478630413	None	None	N
L/Q	0.8532	likely_pathogenic	0.8844	pathogenic	-2.29	Highly Destabilizing	0.971	D	0.621	neutral	N	0.500090963	None	None	N
L/R	0.8939	likely_pathogenic	0.926	pathogenic	-1.232	Destabilizing	0.971	D	0.611	neutral	N	0.488734657	None	None	N
L/S	0.8588	likely_pathogenic	0.8896	pathogenic	-2.602	Highly Destabilizing	0.956	D	0.618	neutral	None	None	None	None	N
L/T	0.5	ambiguous	0.5498	ambiguous	-2.413	Highly Destabilizing	0.86	D	0.597	neutral	None	None	None	None	N
L/V	0.1542	likely_benign	0.1779	benign	-1.388	Destabilizing	0.058	N	0.29	neutral	N	0.380671431	None	None	N
L/W	0.9149	likely_pathogenic	0.9369	pathogenic	-1.698	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	N
L/Y	0.9549	likely_pathogenic	0.9687	pathogenic	-1.413	Destabilizing	0.993	D	0.591	neutral	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.