TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24626	74101;74102;74103	chr2:178572256;178572255;178572254	chr2:179436983;179436982;179436981
N2AB	22985	69178;69179;69180	chr2:178572256;178572255;178572254	chr2:179436983;179436982;179436981
N2A	22058	66397;66398;66399	chr2:178572256;178572255;178572254	chr2:179436983;179436982;179436981
N2B	15561	46906;46907;46908	chr2:178572256;178572255;178572254	chr2:179436983;179436982;179436981
Novex-1	15686	47281;47282;47283	chr2:178572256;178572255;178572254	chr2:179436983;179436982;179436981
Novex-2	15753	47482;47483;47484	chr2:178572256;178572255;178572254	chr2:179436983;179436982;179436981
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-67
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3855
• 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
M/I	rs1060500561	None	None	N	0.051	0.177	0.21737058555	gnomAD-4.0.0	2.73769E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.47343E-04	8.99627E-07	0	1.65722E-05

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
M/A	0.1679	likely_benign	0.1429	benign	-0.248	Destabilizing	None	N	0.154	neutral	None	None	None	None	N
M/C	0.5349	ambiguous	0.5053	ambiguous	-0.437	Destabilizing	0.114	N	0.367	neutral	None	None	None	None	N
M/D	0.5434	ambiguous	0.5188	ambiguous	0.645	Stabilizing	0.001	N	0.336	neutral	None	None	None	None	N
M/E	0.2808	likely_benign	0.2401	benign	0.593	Stabilizing	None	N	0.283	neutral	None	None	None	None	N
M/F	0.3331	likely_benign	0.243	benign	0.055	Stabilizing	None	N	0.2	neutral	None	None	None	None	N
M/G	0.3429	ambiguous	0.2905	benign	-0.414	Destabilizing	0.003	N	0.302	neutral	None	None	None	None	N
M/H	0.2666	likely_benign	0.2575	benign	0.376	Stabilizing	0.14	N	0.424	neutral	None	None	None	None	N
M/I	0.1602	likely_benign	0.1096	benign	0.088	Stabilizing	None	N	0.051	neutral	N	0.371774228	None	None	N
M/K	0.0879	likely_benign	0.0861	benign	0.653	Stabilizing	None	N	0.103	neutral	N	0.366232336	None	None	N
M/L	0.0884	likely_benign	0.0767	benign	0.088	Stabilizing	None	N	0.046	neutral	N	0.363058744	None	None	N
M/N	0.23	likely_benign	0.2152	benign	0.728	Stabilizing	0.002	N	0.32	neutral	None	None	None	None	N
M/P	0.833	likely_pathogenic	0.7934	pathogenic	0.006	Stabilizing	0.005	N	0.317	neutral	None	None	None	None	N
M/Q	0.1196	likely_benign	0.1167	benign	0.583	Stabilizing	0.003	N	0.22	neutral	None	None	None	None	N
M/R	0.102	likely_benign	0.0945	benign	1.076	Stabilizing	None	N	0.13	neutral	N	0.419989463	None	None	N
M/S	0.1731	likely_benign	0.1582	benign	0.237	Stabilizing	0.001	N	0.244	neutral	None	None	None	None	N
M/T	0.0697	likely_benign	0.0705	benign	0.293	Stabilizing	None	N	0.102	neutral	N	0.304509086	None	None	N
M/V	0.0656	likely_benign	0.0548	benign	0.006	Stabilizing	None	N	0.056	neutral	N	0.330023606	None	None	N
M/W	0.552	ambiguous	0.4687	ambiguous	0.058	Stabilizing	0.369	N	0.282	neutral	None	None	None	None	N
M/Y	0.5128	ambiguous	0.4463	ambiguous	0.251	Stabilizing	0.008	N	0.297	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.