TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31336	94231;94232;94233	chr2:178547620;178547619;178547618	chr2:179412347;179412346;179412345
N2AB	29695	89308;89309;89310	chr2:178547620;178547619;178547618	chr2:179412347;179412346;179412345
N2A	28768	86527;86528;86529	chr2:178547620;178547619;178547618	chr2:179412347;179412346;179412345
N2B	22271	67036;67037;67038	chr2:178547620;178547619;178547618	chr2:179412347;179412346;179412345
Novex-1	22396	67411;67412;67413	chr2:178547620;178547619;178547618	chr2:179412347;179412346;179412345
Novex-2	22463	67612;67613;67614	chr2:178547620;178547619;178547618	chr2:179412347;179412346;179412345
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-116
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.1983
• 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
G/R	None	None	0.001	N	0.486	0.11	0.256283259241	gnomAD-4.0.0	3.18214E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	None	0	0	0	1.43271E-05	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
G/A	0.079	likely_benign	0.088	benign	-0.579	Destabilizing	0.001	N	0.188	neutral	N	0.375641253	None	None	N
G/C	0.1494	likely_benign	0.1734	benign	-1.021	Destabilizing	0.316	N	0.599	neutral	None	None	None	None	N
G/D	0.0482	likely_benign	0.0433	benign	-1.073	Destabilizing	None	N	0.182	neutral	None	None	None	None	N
G/E	0.1328	likely_benign	0.1631	benign	-1.213	Destabilizing	None	N	0.215	neutral	N	0.38158579	None	None	N
G/F	0.4209	ambiguous	0.4957	ambiguous	-1.344	Destabilizing	0.051	N	0.588	neutral	None	None	None	None	N
G/H	0.2498	likely_benign	0.2672	benign	-0.882	Destabilizing	0.009	N	0.559	neutral	None	None	None	None	N
G/I	0.1734	likely_benign	0.189	benign	-0.6	Destabilizing	0.008	N	0.569	neutral	None	None	None	None	N
G/K	0.3334	likely_benign	0.3721	ambiguous	-0.877	Destabilizing	None	N	0.271	neutral	None	None	None	None	N
G/L	0.25	likely_benign	0.2938	benign	-0.6	Destabilizing	0.002	N	0.501	neutral	None	None	None	None	N
G/M	0.3219	likely_benign	0.3589	ambiguous	-0.459	Destabilizing	0.116	N	0.583	neutral	None	None	None	None	N
G/N	0.0751	likely_benign	0.0689	benign	-0.596	Destabilizing	None	N	0.116	neutral	None	None	None	None	N
G/P	0.5984	likely_pathogenic	0.6563	pathogenic	-0.56	Destabilizing	0.003	N	0.477	neutral	None	None	None	None	N
G/Q	0.235	likely_benign	0.2801	benign	-0.939	Destabilizing	0.002	N	0.478	neutral	None	None	None	None	N
G/R	0.2603	likely_benign	0.3138	benign	-0.453	Destabilizing	0.001	N	0.486	neutral	N	0.379124275	None	None	N
G/S	0.0547	likely_benign	0.0538	benign	-0.756	Destabilizing	None	N	0.173	neutral	None	None	None	None	N
G/T	0.0779	likely_benign	0.0763	benign	-0.835	Destabilizing	None	N	0.266	neutral	None	None	None	None	N
G/V	0.1155	likely_benign	0.133	benign	-0.56	Destabilizing	0.003	N	0.51	neutral	N	0.436593711	None	None	N
G/W	0.4701	ambiguous	0.5503	ambiguous	-1.487	Destabilizing	0.316	N	0.563	neutral	None	None	None	None	N
G/Y	0.2343	likely_benign	0.2511	benign	-1.117	Destabilizing	0.051	N	0.589	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.