TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21524	64795;64796;64797	chr2:178585174;178585173;178585172	chr2:179449901;179449900;179449899
N2AB	19883	59872;59873;59874	chr2:178585174;178585173;178585172	chr2:179449901;179449900;179449899
N2A	18956	57091;57092;57093	chr2:178585174;178585173;178585172	chr2:179449901;179449900;179449899
N2B	12459	37600;37601;37602	chr2:178585174;178585173;178585172	chr2:179449901;179449900;179449899
Novex-1	12584	37975;37976;37977	chr2:178585174;178585173;178585172	chr2:179449901;179449900;179449899
Novex-2	12651	38176;38177;38178	chr2:178585174;178585173;178585172	chr2:179449901;179449900;179449899
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-124
• Domain position: 56
• Structural Position: 138
• Q(SASA): 0.1193
• 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/V	rs1378663120	-0.952	0.898	N	0.705	0.501	0.732481921647	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	1.11421E-04	None	0	None	0	0	0
L/V	rs1378663120	-0.952	0.898	N	0.705	0.501	0.732481921647	gnomAD-4.0.0	3.18443E-06	None	None	None	None	N	None	0	0	None	0	5.54785E-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	0.9716	likely_pathogenic	0.9545	pathogenic	-2.298	Highly Destabilizing	0.983	D	0.713	prob.delet.	None	None	None	None	N
L/C	0.9466	likely_pathogenic	0.92	pathogenic	-1.393	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9996	pathogenic	-3.118	Highly Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
L/E	0.9987	likely_pathogenic	0.9978	pathogenic	-2.796	Highly Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
L/F	0.5983	likely_pathogenic	0.4127	ambiguous	-1.45	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/G	0.9959	likely_pathogenic	0.9924	pathogenic	-2.878	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/H	0.9933	likely_pathogenic	0.9867	pathogenic	-2.809	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/I	0.2191	likely_benign	0.1999	benign	-0.546	Destabilizing	0.289	N	0.415	neutral	None	None	None	None	N
L/K	0.9963	likely_pathogenic	0.9939	pathogenic	-1.811	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
L/M	0.3845	ambiguous	0.3262	benign	-0.688	Destabilizing	0.993	D	0.774	deleterious	D	0.531422217	None	None	N
L/N	0.9985	likely_pathogenic	0.9971	pathogenic	-2.611	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9968	pathogenic	-1.123	Destabilizing	0.999	D	0.897	deleterious	D	0.562403715	None	None	N
L/Q	0.9922	likely_pathogenic	0.9873	pathogenic	-2.176	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.562403715	None	None	N
L/R	0.9913	likely_pathogenic	0.9859	pathogenic	-2.106	Highly Destabilizing	0.999	D	0.891	deleterious	D	0.562403715	None	None	N
L/S	0.9972	likely_pathogenic	0.9948	pathogenic	-3.032	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
L/T	0.9872	likely_pathogenic	0.9795	pathogenic	-2.542	Highly Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
L/V	0.3216	likely_benign	0.2782	benign	-1.123	Destabilizing	0.898	D	0.705	prob.neutral	N	0.517179076	None	None	N
L/W	0.9662	likely_pathogenic	0.9299	pathogenic	-1.831	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/Y	0.9682	likely_pathogenic	0.9247	pathogenic	-1.607	Destabilizing	0.999	D	0.817	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.