TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6034	18325;18326;18327	chr2:178730300;178730299;178730298	chr2:179595027;179595026;179595025
N2AB	5717	17374;17375;17376	chr2:178730300;178730299;178730298	chr2:179595027;179595026;179595025
N2A	4790	14593;14594;14595	chr2:178730300;178730299;178730298	chr2:179595027;179595026;179595025
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-44
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3347
• 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/H	None	None	1.0	N	0.786	0.43	0.848622260122	gnomAD-4.0.0	6.8506E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.1636E-05	0
L/P	None	None	0.999	N	0.786	0.498	0.84006711756	gnomAD-4.0.0	6.8506E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87631E-05	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	0.1394	likely_benign	0.1662	benign	-1.305	Destabilizing	0.983	D	0.647	neutral	None	None	None	None	N
L/C	0.4448	ambiguous	0.4519	ambiguous	-0.935	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/D	0.5101	ambiguous	0.5895	pathogenic	-0.349	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
L/E	0.2323	likely_benign	0.273	benign	-0.38	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
L/F	0.0934	likely_benign	0.1068	benign	-1.042	Destabilizing	0.993	D	0.757	deleterious	N	0.51433771	None	None	N
L/G	0.4471	ambiguous	0.488	ambiguous	-1.566	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
L/H	0.1265	likely_benign	0.1553	benign	-0.765	Destabilizing	1.0	D	0.786	deleterious	N	0.497752105	None	None	N
L/I	0.064	likely_benign	0.0707	benign	-0.692	Destabilizing	0.235	N	0.331	neutral	N	0.458599071	None	None	N
L/K	0.1403	likely_benign	0.1656	benign	-0.645	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
L/M	0.0894	likely_benign	0.0977	benign	-0.568	Destabilizing	0.995	D	0.746	deleterious	None	None	None	None	N
L/N	0.2381	likely_benign	0.2891	benign	-0.453	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
L/P	0.713	likely_pathogenic	0.6512	pathogenic	-0.864	Destabilizing	0.999	D	0.786	deleterious	N	0.484188162	None	None	N
L/Q	0.0907	likely_benign	0.1083	benign	-0.665	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/R	0.1012	likely_benign	0.1159	benign	-0.116	Destabilizing	0.999	D	0.799	deleterious	N	0.42748673	None	None	N
L/S	0.1461	likely_benign	0.1877	benign	-1.118	Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
L/T	0.1135	likely_benign	0.1404	benign	-1.033	Destabilizing	0.995	D	0.772	deleterious	None	None	None	None	N
L/V	0.0596	likely_benign	0.0667	benign	-0.864	Destabilizing	0.898	D	0.582	neutral	N	0.441360104	None	None	N
L/W	0.1822	likely_benign	0.198	benign	-1.029	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/Y	0.2433	likely_benign	0.2714	benign	-0.778	Destabilizing	0.999	D	0.813	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.