TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2545	7858;7859;7860	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056
N2AB	2545	7858;7859;7860	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056
N2A	2545	7858;7859;7860	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056
N2B	2499	7720;7721;7722	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056
Novex-1	2499	7720;7721;7722	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056
Novex-2	2499	7720;7721;7722	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056
Novex-3	2545	7858;7859;7860	chr2:178773331;178773330;178773329	chr2:179638058;179638057;179638056

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-15
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.3959
• 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
T/A	rs761827668	-0.717	0.201	N	0.317	0.172	0.166414681773	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/A	rs761827668	-0.717	0.201	N	0.317	0.172	0.166414681773	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
T/A	rs761827668	-0.717	0.201	N	0.317	0.172	0.166414681773	gnomAD-4.0.0	2.56155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78357E-06	0	0
T/I	rs1016165797	-0.161	0.379	N	0.359	0.405	0.405700215632	gnomAD-2.1.1	1.06E-05	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	1.55E-05	0
T/I	rs1016165797	-0.161	0.379	N	0.359	0.405	0.405700215632	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	0
T/I	rs1016165797	-0.161	0.379	N	0.359	0.405	0.405700215632	gnomAD-4.0.0	1.67306E-05	None	None	None	None	N	None	0	1.66756E-05	None	0	0	None	0	0	2.11869E-05	0	1.60056E-05
T/R	None	None	0.81	N	0.381	0.454	0.610832418033	gnomAD-4.0.0	1.36826E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79863E-06	0	0
T/S	rs761827668	-0.764	0.007	N	0.213	0.094	0.128392430309	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/S	rs761827668	-0.764	0.007	N	0.213	0.094	0.128392430309	gnomAD-4.0.0	1.59081E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
T/A	0.1175	likely_benign	0.1372	benign	-0.355	Destabilizing	0.201	N	0.317	neutral	N	0.508829196	None	None	N
T/C	0.6431	likely_pathogenic	0.7035	pathogenic	-0.257	Destabilizing	0.992	D	0.399	neutral	None	None	None	None	N
T/D	0.5443	ambiguous	0.6428	pathogenic	-0.028	Destabilizing	0.617	D	0.367	neutral	None	None	None	None	N
T/E	0.3921	ambiguous	0.4563	ambiguous	-0.105	Destabilizing	0.617	D	0.379	neutral	None	None	None	None	N
T/F	0.3804	ambiguous	0.4865	ambiguous	-0.789	Destabilizing	0.85	D	0.522	neutral	None	None	None	None	N
T/G	0.3779	ambiguous	0.4602	ambiguous	-0.496	Destabilizing	0.447	N	0.445	neutral	None	None	None	None	N
T/H	0.4007	ambiguous	0.4733	ambiguous	-0.821	Destabilizing	0.977	D	0.521	neutral	None	None	None	None	N
T/I	0.308	likely_benign	0.3706	ambiguous	-0.102	Destabilizing	0.379	N	0.359	neutral	N	0.508354036	None	None	N
T/K	0.2345	likely_benign	0.2814	benign	-0.471	Destabilizing	0.379	N	0.373	neutral	N	0.46749623	None	None	N
T/L	0.1359	likely_benign	0.1693	benign	-0.102	Destabilizing	0.25	N	0.344	neutral	None	None	None	None	N
T/M	0.1232	likely_benign	0.1439	benign	0.11	Stabilizing	0.127	N	0.346	neutral	None	None	None	None	N
T/N	0.1964	likely_benign	0.2522	benign	-0.228	Destabilizing	0.447	N	0.329	neutral	None	None	None	None	N
T/P	0.1948	likely_benign	0.2213	benign	-0.157	Destabilizing	0.896	D	0.381	neutral	N	0.511413645	None	None	N
T/Q	0.3018	likely_benign	0.3472	ambiguous	-0.49	Destabilizing	0.85	D	0.397	neutral	None	None	None	None	N
T/R	0.2121	likely_benign	0.2517	benign	-0.168	Destabilizing	0.81	D	0.381	neutral	N	0.508829196	None	None	N
T/S	0.1475	likely_benign	0.1826	benign	-0.418	Destabilizing	0.007	N	0.213	neutral	N	0.492192094	None	None	N
T/V	0.234	likely_benign	0.2777	benign	-0.157	Destabilizing	0.447	N	0.29	neutral	None	None	None	None	N
T/W	0.7308	likely_pathogenic	0.7939	pathogenic	-0.785	Destabilizing	0.992	D	0.571	neutral	None	None	None	None	N
T/Y	0.4421	ambiguous	0.5292	ambiguous	-0.517	Destabilizing	0.972	D	0.523	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.