TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28248	84967;84968;84969	chr2:178561390;178561389;178561388	chr2:179426117;179426116;179426115
N2AB	26607	80044;80045;80046	chr2:178561390;178561389;178561388	chr2:179426117;179426116;179426115
N2A	25680	77263;77264;77265	chr2:178561390;178561389;178561388	chr2:179426117;179426116;179426115
N2B	19183	57772;57773;57774	chr2:178561390;178561389;178561388	chr2:179426117;179426116;179426115
Novex-1	19308	58147;58148;58149	chr2:178561390;178561389;178561388	chr2:179426117;179426116;179426115
Novex-2	19375	58348;58349;58350	chr2:178561390;178561389;178561388	chr2:179426117;179426116;179426115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-93
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3082
• 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
P/L	None	None	0.049	N	0.381	0.139	0.277730125212	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/T	None	None	0.049	N	0.393	0.046	0.139678290688	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.0535	likely_benign	0.0516	benign	-1.233	Destabilizing	None	N	0.231	neutral	N	0.331636972	None	None	N
P/C	0.4374	ambiguous	0.3818	ambiguous	-0.697	Destabilizing	0.703	D	0.482	neutral	None	None	None	None	N
P/D	0.7228	likely_pathogenic	0.6849	pathogenic	-1.209	Destabilizing	0.25	N	0.534	neutral	None	None	None	None	N
P/E	0.4242	ambiguous	0.3774	ambiguous	-1.275	Destabilizing	0.25	N	0.47	neutral	None	None	None	None	N
P/F	0.3784	ambiguous	0.3345	benign	-1.171	Destabilizing	0.538	D	0.53	neutral	None	None	None	None	N
P/G	0.3715	ambiguous	0.3517	ambiguous	-1.478	Destabilizing	0.064	N	0.421	neutral	None	None	None	None	N
P/H	0.3166	likely_benign	0.2672	benign	-1.057	Destabilizing	0.845	D	0.434	neutral	N	0.434686769	None	None	N
P/I	0.2037	likely_benign	0.1852	benign	-0.685	Destabilizing	0.143	N	0.451	neutral	None	None	None	None	N
P/K	0.4388	ambiguous	0.3821	ambiguous	-1.063	Destabilizing	0.25	N	0.457	neutral	None	None	None	None	N
P/L	0.0943	likely_benign	0.0856	benign	-0.685	Destabilizing	0.049	N	0.381	neutral	N	0.356724631	None	None	N
P/M	0.22	likely_benign	0.2059	benign	-0.405	Destabilizing	0.703	D	0.449	neutral	None	None	None	None	N
P/N	0.5043	ambiguous	0.4706	ambiguous	-0.713	Destabilizing	0.25	N	0.519	neutral	None	None	None	None	N
P/Q	0.2278	likely_benign	0.1948	benign	-0.977	Destabilizing	0.703	D	0.485	neutral	None	None	None	None	N
P/R	0.3003	likely_benign	0.2433	benign	-0.445	Destabilizing	0.201	N	0.539	neutral	N	0.415580934	None	None	N
P/S	0.147	likely_benign	0.1389	benign	-1.116	Destabilizing	0.004	N	0.263	neutral	N	0.385778102	None	None	N
P/T	0.1073	likely_benign	0.1028	benign	-1.086	Destabilizing	0.049	N	0.393	neutral	N	0.40552615	None	None	N
P/V	0.1258	likely_benign	0.1188	benign	-0.833	Destabilizing	None	N	0.327	neutral	None	None	None	None	N
P/W	0.6377	likely_pathogenic	0.5768	pathogenic	-1.303	Destabilizing	0.964	D	0.578	neutral	None	None	None	None	N
P/Y	0.4193	ambiguous	0.3689	ambiguous	-1.035	Destabilizing	0.703	D	0.518	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.