TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25347	76264;76265;76266	chr2:178570093;178570092;178570091	chr2:179434820;179434819;179434818
N2AB	23706	71341;71342;71343	chr2:178570093;178570092;178570091	chr2:179434820;179434819;179434818
N2A	22779	68560;68561;68562	chr2:178570093;178570092;178570091	chr2:179434820;179434819;179434818
N2B	16282	49069;49070;49071	chr2:178570093;178570092;178570091	chr2:179434820;179434819;179434818
Novex-1	16407	49444;49445;49446	chr2:178570093;178570092;178570091	chr2:179434820;179434819;179434818
Novex-2	16474	49645;49646;49647	chr2:178570093;178570092;178570091	chr2:179434820;179434819;179434818
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-72
• Domain position: 44
• Structural Position: 54
• Q(SASA): 1.0317
• Predicted PPI site: I

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
E/D	rs1310471153	0.076	0.001	N	0.228	0.063	0.0611884634855	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/D	rs1310471153	0.076	0.001	N	0.228	0.063	0.0611884634855	gnomAD-4.0.0	8.21205E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.39134E-04	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
E/A	0.1266	likely_benign	0.1121	benign	-0.186	Destabilizing	0.521	D	0.412	neutral	N	0.440020805	None	None	I
E/C	0.8143	likely_pathogenic	0.7799	pathogenic	-0.063	Destabilizing	0.996	D	0.414	neutral	None	None	None	None	I
E/D	0.1172	likely_benign	0.1098	benign	-0.051	Destabilizing	0.001	N	0.228	neutral	N	0.424933922	None	None	I
E/F	0.765	likely_pathogenic	0.7119	pathogenic	-0.214	Destabilizing	0.953	D	0.381	neutral	None	None	None	None	I
E/G	0.159	likely_benign	0.1376	benign	-0.333	Destabilizing	0.684	D	0.441	neutral	N	0.426048643	None	None	I
E/H	0.5031	ambiguous	0.4289	ambiguous	0.208	Stabilizing	0.984	D	0.338	neutral	None	None	None	None	I
E/I	0.4194	ambiguous	0.384	ambiguous	0.153	Stabilizing	0.91	D	0.406	neutral	None	None	None	None	I
E/K	0.2154	likely_benign	0.1669	benign	0.277	Stabilizing	0.684	D	0.434	neutral	N	0.41148741	None	None	I
E/L	0.4003	ambiguous	0.3567	ambiguous	0.153	Stabilizing	0.59	D	0.409	neutral	None	None	None	None	I
E/M	0.4646	ambiguous	0.4111	ambiguous	0.079	Stabilizing	0.996	D	0.397	neutral	None	None	None	None	I
E/N	0.2535	likely_benign	0.2137	benign	0.227	Stabilizing	0.742	D	0.379	neutral	None	None	None	None	I
E/P	0.7822	likely_pathogenic	0.7646	pathogenic	0.059	Stabilizing	0.953	D	0.383	neutral	None	None	None	None	I
E/Q	0.1702	likely_benign	0.1448	benign	0.239	Stabilizing	0.815	D	0.395	neutral	N	0.485387735	None	None	I
E/R	0.3393	likely_benign	0.2748	benign	0.507	Stabilizing	0.91	D	0.349	neutral	None	None	None	None	I
E/S	0.1849	likely_benign	0.1611	benign	-0.006	Destabilizing	0.59	D	0.399	neutral	None	None	None	None	I
E/T	0.1826	likely_benign	0.1609	benign	0.11	Stabilizing	0.009	N	0.292	neutral	None	None	None	None	I
E/V	0.2318	likely_benign	0.2143	benign	0.059	Stabilizing	0.521	D	0.403	neutral	N	0.496490163	None	None	I
E/W	0.8989	likely_pathogenic	0.8682	pathogenic	-0.145	Destabilizing	0.996	D	0.486	neutral	None	None	None	None	I
E/Y	0.5938	likely_pathogenic	0.5447	ambiguous	0.008	Stabilizing	0.984	D	0.388	neutral	None	None	None	None	I

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.