TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1124	3595;3596;3597	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947
N2AB	1124	3595;3596;3597	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947
N2A	1124	3595;3596;3597	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947
N2B	1078	3457;3458;3459	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947
Novex-1	1078	3457;3458;3459	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947
Novex-2	1078	3457;3458;3459	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947
Novex-3	1124	3595;3596;3597	chr2:178782222;178782221;178782220	chr2:179646949;179646948;179646947

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-4
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.6407
• 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	rs2092846515	None	0.223	N	0.473	0.139	0.149567049428	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	0	0
T/S	None	None	0.004	N	0.329	0.135	0.12205267543	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-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
T/A	0.1071	likely_benign	0.0884	benign	-0.194	Destabilizing	0.223	N	0.473	neutral	N	0.442353121	None	None	N
T/C	0.7622	likely_pathogenic	0.6602	pathogenic	-0.252	Destabilizing	0.98	D	0.641	neutral	None	None	None	None	N
T/D	0.7062	likely_pathogenic	0.59	pathogenic	0.323	Stabilizing	0.764	D	0.624	neutral	None	None	None	None	N
T/E	0.7097	likely_pathogenic	0.5907	pathogenic	0.237	Stabilizing	0.764	D	0.617	neutral	None	None	None	None	N
T/F	0.7213	likely_pathogenic	0.6173	pathogenic	-0.808	Destabilizing	0.929	D	0.69	prob.neutral	None	None	None	None	N
T/G	0.2672	likely_benign	0.2209	benign	-0.28	Destabilizing	0.48	N	0.568	neutral	None	None	None	None	N
T/H	0.6126	likely_pathogenic	0.4944	ambiguous	-0.57	Destabilizing	0.98	D	0.647	neutral	None	None	None	None	N
T/I	0.6857	likely_pathogenic	0.5628	ambiguous	-0.094	Destabilizing	0.83	D	0.665	neutral	N	0.478245249	None	None	N
T/K	0.6346	likely_pathogenic	0.523	ambiguous	-0.189	Destabilizing	0.764	D	0.626	neutral	None	None	None	None	N
T/L	0.3501	ambiguous	0.276	benign	-0.094	Destabilizing	0.648	D	0.585	neutral	None	None	None	None	N
T/M	0.2542	likely_benign	0.2034	benign	-0.035	Destabilizing	0.993	D	0.665	neutral	None	None	None	None	N
T/N	0.2324	likely_benign	0.1816	benign	-0.002	Destabilizing	0.709	D	0.609	neutral	N	0.421744186	None	None	N
T/P	0.2075	likely_benign	0.1596	benign	-0.101	Destabilizing	0.83	D	0.658	neutral	N	0.427455694	None	None	N
T/Q	0.5533	ambiguous	0.4567	ambiguous	-0.198	Destabilizing	0.866	D	0.663	neutral	None	None	None	None	N
T/R	0.5778	likely_pathogenic	0.4655	ambiguous	0.011	Stabilizing	0.866	D	0.653	neutral	None	None	None	None	N
T/S	0.0962	likely_benign	0.0845	benign	-0.194	Destabilizing	0.004	N	0.329	neutral	N	0.424626715	None	None	N
T/V	0.434	ambiguous	0.36	ambiguous	-0.101	Destabilizing	0.648	D	0.54	neutral	None	None	None	None	N
T/W	0.9003	likely_pathogenic	0.8495	pathogenic	-0.866	Destabilizing	0.993	D	0.669	neutral	None	None	None	None	N
T/Y	0.6907	likely_pathogenic	0.595	pathogenic	-0.543	Destabilizing	0.929	D	0.679	prob.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.