TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33757	101494;101495;101496	chr2:178535346;178535345;178535344	chr2:179400073;179400072;179400071
N2AB	32116	96571;96572;96573	chr2:178535346;178535345;178535344	chr2:179400073;179400072;179400071
N2A	31189	93790;93791;93792	chr2:178535346;178535345;178535344	chr2:179400073;179400072;179400071
N2B	24692	74299;74300;74301	chr2:178535346;178535345;178535344	chr2:179400073;179400072;179400071
Novex-1	24817	74674;74675;74676	chr2:178535346;178535345;178535344	chr2:179400073;179400072;179400071
Novex-2	24884	74875;74876;74877	chr2:178535346;178535345;178535344	chr2:179400073;179400072;179400071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-132
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.215
• 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
S/N	rs1210718667	-0.362	0.342	N	0.407	0.105	0.18274738541	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
S/N	rs1210718667	-0.362	0.342	N	0.407	0.105	0.18274738541	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs1210718667	-0.362	0.342	N	0.407	0.105	0.18274738541	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46968E-05	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
S/A	0.0814	likely_benign	0.0917	benign	-0.84	Destabilizing	0.082	N	0.299	neutral	None	None	None	None	N
S/C	0.131	likely_benign	0.1617	benign	-0.686	Destabilizing	0.997	D	0.463	neutral	N	0.468116782	None	None	N
S/D	0.6626	likely_pathogenic	0.712	pathogenic	-0.913	Destabilizing	0.854	D	0.39	neutral	None	None	None	None	N
S/E	0.5798	likely_pathogenic	0.6588	pathogenic	-0.875	Destabilizing	0.772	D	0.397	neutral	None	None	None	None	N
S/F	0.4858	ambiguous	0.5134	ambiguous	-0.985	Destabilizing	0.994	D	0.591	neutral	None	None	None	None	N
S/G	0.1375	likely_benign	0.1561	benign	-1.106	Destabilizing	0.772	D	0.405	neutral	N	0.485734452	None	None	N
S/H	0.4279	ambiguous	0.5274	ambiguous	-1.564	Destabilizing	0.994	D	0.481	neutral	None	None	None	None	N
S/I	0.2737	likely_benign	0.3467	ambiguous	-0.224	Destabilizing	0.983	D	0.523	neutral	N	0.48338758	None	None	N
S/K	0.6308	likely_pathogenic	0.7625	pathogenic	-0.671	Destabilizing	0.11	N	0.124	neutral	None	None	None	None	N
S/L	0.1773	likely_benign	0.2108	benign	-0.224	Destabilizing	0.917	D	0.427	neutral	None	None	None	None	N
S/M	0.2782	likely_benign	0.3533	ambiguous	0.049	Stabilizing	0.998	D	0.48	neutral	None	None	None	None	N
S/N	0.1774	likely_benign	0.221	benign	-0.824	Destabilizing	0.342	N	0.407	neutral	N	0.441076811	None	None	N
S/P	0.4	ambiguous	0.4739	ambiguous	-0.396	Destabilizing	0.977	D	0.452	neutral	None	None	None	None	N
S/Q	0.447	ambiguous	0.5555	ambiguous	-0.984	Destabilizing	0.956	D	0.441	neutral	None	None	None	None	N
S/R	0.5543	ambiguous	0.655	pathogenic	-0.608	Destabilizing	0.049	N	0.318	neutral	N	0.471303717	None	None	N
S/T	0.0962	likely_benign	0.1162	benign	-0.751	Destabilizing	0.007	N	0.117	neutral	N	0.429841097	None	None	N
S/V	0.248	likely_benign	0.3174	benign	-0.396	Destabilizing	0.804	D	0.465	neutral	None	None	None	None	N
S/W	0.6531	likely_pathogenic	0.6806	pathogenic	-0.996	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
S/Y	0.3798	ambiguous	0.4087	ambiguous	-0.688	Destabilizing	0.998	D	0.591	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.