TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23305	70138;70139;70140	chr2:178576219;178576218;178576217	chr2:179440946;179440945;179440944
N2AB	21664	65215;65216;65217	chr2:178576219;178576218;178576217	chr2:179440946;179440945;179440944
N2A	20737	62434;62435;62436	chr2:178576219;178576218;178576217	chr2:179440946;179440945;179440944
N2B	14240	42943;42944;42945	chr2:178576219;178576218;178576217	chr2:179440946;179440945;179440944
Novex-1	14365	43318;43319;43320	chr2:178576219;178576218;178576217	chr2:179440946;179440945;179440944
Novex-2	14432	43519;43520;43521	chr2:178576219;178576218;178576217	chr2:179440946;179440945;179440944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-57
• Domain position: 66
• Structural Position: 96
• Q(SASA): 0.9716
• 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
D/N	None	None	None	N	0.163	0.176	0.219573609325	gnomAD-4.0.0	2.05367E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69921E-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
D/A	0.1426	likely_benign	0.1362	benign	-0.109	Destabilizing	0.012	N	0.247	neutral	N	0.508363383	None	None	N
D/C	0.5128	ambiguous	0.489	ambiguous	-0.189	Destabilizing	0.864	D	0.36	neutral	None	None	None	None	N
D/E	0.1371	likely_benign	0.1311	benign	-0.276	Destabilizing	None	N	0.155	neutral	N	0.44662149	None	None	N
D/F	0.5217	ambiguous	0.5271	ambiguous	-0.065	Destabilizing	0.356	N	0.389	neutral	None	None	None	None	N
D/G	0.1157	likely_benign	0.1213	benign	-0.266	Destabilizing	None	N	0.167	neutral	N	0.369963287	None	None	N
D/H	0.1939	likely_benign	0.2023	benign	0.432	Stabilizing	None	N	0.189	neutral	N	0.463188453	None	None	N
D/I	0.3881	ambiguous	0.3661	ambiguous	0.248	Stabilizing	0.356	N	0.429	neutral	None	None	None	None	N
D/K	0.2914	likely_benign	0.2946	benign	0.304	Stabilizing	None	N	0.153	neutral	None	None	None	None	N
D/L	0.3318	likely_benign	0.32	benign	0.248	Stabilizing	0.072	N	0.343	neutral	None	None	None	None	N
D/M	0.509	ambiguous	0.4917	ambiguous	0.088	Stabilizing	0.628	D	0.384	neutral	None	None	None	None	N
D/N	0.069	likely_benign	0.0711	benign	0.019	Stabilizing	None	N	0.163	neutral	N	0.385282243	None	None	N
D/P	0.7593	likely_pathogenic	0.695	pathogenic	0.15	Stabilizing	None	N	0.208	neutral	None	None	None	None	N
D/Q	0.2373	likely_benign	0.2354	benign	0.039	Stabilizing	0.038	N	0.27	neutral	None	None	None	None	N
D/R	0.3507	ambiguous	0.3558	ambiguous	0.596	Stabilizing	0.038	N	0.294	neutral	None	None	None	None	N
D/S	0.0995	likely_benign	0.098	benign	-0.092	Destabilizing	0.016	N	0.22	neutral	None	None	None	None	N
D/T	0.211	likely_benign	0.2037	benign	0.033	Stabilizing	0.031	N	0.247	neutral	None	None	None	None	N
D/V	0.2434	likely_benign	0.2272	benign	0.15	Stabilizing	0.055	N	0.387	neutral	N	0.485401797	None	None	N
D/W	0.8616	likely_pathogenic	0.8671	pathogenic	0.03	Stabilizing	0.864	D	0.373	neutral	None	None	None	None	N
D/Y	0.2133	likely_benign	0.2217	benign	0.168	Stabilizing	0.171	N	0.417	neutral	N	0.473792002	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.