TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15926	48001;48002;48003	chr2:178617219;178617218;178617217	chr2:179481946;179481945;179481944
N2AB	14285	43078;43079;43080	chr2:178617219;178617218;178617217	chr2:179481946;179481945;179481944
N2A	13358	40297;40298;40299	chr2:178617219;178617218;178617217	chr2:179481946;179481945;179481944
N2B	6861	20806;20807;20808	chr2:178617219;178617218;178617217	chr2:179481946;179481945;179481944
Novex-1	6986	21181;21182;21183	chr2:178617219;178617218;178617217	chr2:179481946;179481945;179481944
Novex-2	7053	21382;21383;21384	chr2:178617219;178617218;178617217	chr2:179481946;179481945;179481944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-3
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.3742
• 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
K/R	None	None	0.025	N	0.32	0.093	0.366466682447	gnomAD-4.0.0	1.20188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31421E-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
K/A	0.1882	likely_benign	0.1886	benign	-0.086	Destabilizing	None	N	0.075	neutral	None	None	None	None	N
K/C	0.6064	likely_pathogenic	0.6131	pathogenic	-0.114	Destabilizing	0.781	D	0.36	neutral	None	None	None	None	N
K/D	0.4271	ambiguous	0.4371	ambiguous	0.022	Stabilizing	0.033	N	0.322	neutral	None	None	None	None	N
K/E	0.1332	likely_benign	0.132	benign	0.024	Stabilizing	0.011	N	0.275	neutral	N	0.346018727	None	None	N
K/F	0.6175	likely_pathogenic	0.629	pathogenic	-0.31	Destabilizing	0.001	N	0.209	neutral	None	None	None	None	N
K/G	0.3603	ambiguous	0.3701	ambiguous	-0.3	Destabilizing	0.033	N	0.278	neutral	None	None	None	None	N
K/H	0.2922	likely_benign	0.2844	benign	-0.675	Destabilizing	0.001	N	0.164	neutral	None	None	None	None	N
K/I	0.2481	likely_benign	0.2474	benign	0.403	Stabilizing	0.111	N	0.434	neutral	N	0.478480436	None	None	N
K/L	0.3028	likely_benign	0.3075	benign	0.403	Stabilizing	0.033	N	0.275	neutral	None	None	None	None	N
K/M	0.1846	likely_benign	0.1875	benign	0.4	Stabilizing	0.54	D	0.353	neutral	None	None	None	None	N
K/N	0.2553	likely_benign	0.2601	benign	0.285	Stabilizing	None	N	0.118	neutral	N	0.444920977	None	None	N
K/P	0.2894	likely_benign	0.2757	benign	0.268	Stabilizing	None	N	0.12	neutral	None	None	None	None	N
K/Q	0.1323	likely_benign	0.1344	benign	0.028	Stabilizing	None	N	0.075	neutral	N	0.431454601	None	None	N
K/R	0.0972	likely_benign	0.0925	benign	-0.001	Destabilizing	0.025	N	0.32	neutral	N	0.469209826	None	None	N
K/S	0.275	likely_benign	0.2788	benign	-0.254	Destabilizing	0.033	N	0.277	neutral	None	None	None	None	N
K/T	0.1362	likely_benign	0.1405	benign	-0.102	Destabilizing	0.049	N	0.326	neutral	N	0.409859533	None	None	N
K/V	0.2408	likely_benign	0.2415	benign	0.268	Stabilizing	0.033	N	0.305	neutral	None	None	None	None	N
K/W	0.7141	likely_pathogenic	0.7168	pathogenic	-0.264	Destabilizing	0.781	D	0.361	neutral	None	None	None	None	N
K/Y	0.462	ambiguous	0.4634	ambiguous	0.091	Stabilizing	0.001	N	0.079	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.