TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26867	80824;80825;80826	chr2:178565533;178565532;178565531	chr2:179430260;179430259;179430258
N2AB	25226	75901;75902;75903	chr2:178565533;178565532;178565531	chr2:179430260;179430259;179430258
N2A	24299	73120;73121;73122	chr2:178565533;178565532;178565531	chr2:179430260;179430259;179430258
N2B	17802	53629;53630;53631	chr2:178565533;178565532;178565531	chr2:179430260;179430259;179430258
Novex-1	17927	54004;54005;54006	chr2:178565533;178565532;178565531	chr2:179430260;179430259;179430258
Novex-2	17994	54205;54206;54207	chr2:178565533;178565532;178565531	chr2:179430260;179430259;179430258
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: Fn3-83
• Domain position: 88
• Structural Position: 123
• Q(SASA): 0.166
• 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/W	rs1038243734	-1.688	1.0	D	0.849	0.693	0.821037014432	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
L/W	rs1038243734	-1.688	1.0	D	0.849	0.693	0.821037014432	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85933E-06	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	0.6103	likely_pathogenic	0.5418	ambiguous	-1.911	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/C	0.8272	likely_pathogenic	0.7966	pathogenic	-1.217	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/D	0.9905	likely_pathogenic	0.9874	pathogenic	-1.721	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/E	0.9583	likely_pathogenic	0.9446	pathogenic	-1.557	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/F	0.6711	likely_pathogenic	0.5915	pathogenic	-1.016	Destabilizing	1.0	D	0.79	deleterious	N	0.494869815	None	None	N
L/G	0.9215	likely_pathogenic	0.8924	pathogenic	-2.394	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/H	0.9292	likely_pathogenic	0.9049	pathogenic	-1.738	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/I	0.2407	likely_benign	0.2091	benign	-0.568	Destabilizing	0.995	D	0.725	deleterious	None	None	None	None	N
L/K	0.9528	likely_pathogenic	0.9467	pathogenic	-1.487	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
L/M	0.3163	likely_benign	0.2826	benign	-0.51	Destabilizing	1.0	D	0.779	deleterious	N	0.483348925	None	None	N
L/N	0.9516	likely_pathogenic	0.9387	pathogenic	-1.654	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/P	0.819	likely_pathogenic	0.7338	pathogenic	-0.99	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/Q	0.8806	likely_pathogenic	0.8534	pathogenic	-1.578	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/R	0.9032	likely_pathogenic	0.8842	pathogenic	-1.169	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/S	0.8454	likely_pathogenic	0.7721	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.848	deleterious	N	0.480448863	None	None	N
L/T	0.524	ambiguous	0.4187	ambiguous	-2.034	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/V	0.2647	likely_benign	0.2256	benign	-0.99	Destabilizing	0.995	D	0.714	prob.delet.	N	0.518412592	None	None	N
L/W	0.8614	likely_pathogenic	0.8237	pathogenic	-1.319	Destabilizing	1.0	D	0.849	deleterious	D	0.527559606	None	None	N
L/Y	0.9436	likely_pathogenic	0.9293	pathogenic	-1.001	Destabilizing	0.999	D	0.797	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.