TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2853	8782;8783;8784	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869
N2AB	2853	8782;8783;8784	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869
N2A	2853	8782;8783;8784	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869
N2B	2807	8644;8645;8646	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869
Novex-1	2807	8644;8645;8646	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869
Novex-2	2807	8644;8645;8646	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869
Novex-3	2853	8782;8783;8784	chr2:178770144;178770143;178770142	chr2:179634871;179634870;179634869

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-18
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.1097
• 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	rs1379690495	-1.968	0.37	N	0.335	0.174	0.385578977469	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/V	rs1379690495	-1.968	0.37	N	0.335	0.174	0.385578977469	gnomAD-4.0.0	1.59047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.9436	likely_pathogenic	0.9361	pathogenic	-3.031	Highly Destabilizing	0.983	D	0.692	prob.neutral	None	None	None	None	N
L/C	0.9133	likely_pathogenic	0.9034	pathogenic	-2.564	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.998	pathogenic	-3.878	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
L/E	0.9897	likely_pathogenic	0.9843	pathogenic	-3.576	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/F	0.5225	ambiguous	0.478	ambiguous	-1.754	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
L/G	0.9908	likely_pathogenic	0.9883	pathogenic	-3.631	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
L/H	0.9524	likely_pathogenic	0.9362	pathogenic	-3.209	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/I	0.1255	likely_benign	0.1253	benign	-1.222	Destabilizing	0.437	N	0.353	neutral	None	None	None	None	N
L/K	0.9708	likely_pathogenic	0.9564	pathogenic	-2.508	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
L/M	0.2684	likely_benign	0.2699	benign	-1.423	Destabilizing	0.997	D	0.692	prob.neutral	D	0.566178997	None	None	N
L/N	0.9918	likely_pathogenic	0.9889	pathogenic	-3.15	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/P	0.9952	likely_pathogenic	0.9927	pathogenic	-1.817	Destabilizing	0.999	D	0.866	deleterious	D	0.611738195	None	None	N
L/Q	0.9338	likely_pathogenic	0.9142	pathogenic	-2.865	Highly Destabilizing	0.999	D	0.859	deleterious	D	0.611738195	None	None	N
L/R	0.9485	likely_pathogenic	0.9214	pathogenic	-2.373	Highly Destabilizing	0.999	D	0.854	deleterious	D	0.611738195	None	None	N
L/S	0.9868	likely_pathogenic	0.9828	pathogenic	-3.752	Highly Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
L/T	0.9551	likely_pathogenic	0.9481	pathogenic	-3.295	Highly Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/V	0.197	likely_benign	0.199	benign	-1.817	Destabilizing	0.37	N	0.335	neutral	N	0.486033241	None	None	N
L/W	0.9071	likely_pathogenic	0.8607	pathogenic	-2.232	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/Y	0.9237	likely_pathogenic	0.9013	pathogenic	-2.048	Highly Destabilizing	0.999	D	0.791	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.