TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16821	50686;50687;50688	chr2:178611848;178611847;178611846	chr2:179476575;179476574;179476573
N2AB	15180	45763;45764;45765	chr2:178611848;178611847;178611846	chr2:179476575;179476574;179476573
N2A	14253	42982;42983;42984	chr2:178611848;178611847;178611846	chr2:179476575;179476574;179476573
N2B	7756	23491;23492;23493	chr2:178611848;178611847;178611846	chr2:179476575;179476574;179476573
Novex-1	7881	23866;23867;23868	chr2:178611848;178611847;178611846	chr2:179476575;179476574;179476573
Novex-2	7948	24067;24068;24069	chr2:178611848;178611847;178611846	chr2:179476575;179476574;179476573
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-10
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3016
• 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
E/G	rs781091773	-1.592	0.477	D	0.633	0.31	0.380730819819	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
E/G	rs781091773	-1.592	0.477	D	0.633	0.31	0.380730819819	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs781091773	-1.592	0.477	D	0.633	0.31	0.380730819819	gnomAD-4.0.0	1.36402E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.86551E-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
E/A	0.391	ambiguous	0.3363	benign	-0.823	Destabilizing	0.477	N	0.554	neutral	N	0.508034959	None	None	N
E/C	0.9694	likely_pathogenic	0.9549	pathogenic	-0.302	Destabilizing	0.985	D	0.746	deleterious	None	None	None	None	N
E/D	0.193	likely_benign	0.1877	benign	-0.79	Destabilizing	0.006	N	0.241	neutral	N	0.503175829	None	None	N
E/F	0.9514	likely_pathogenic	0.9306	pathogenic	-0.353	Destabilizing	0.945	D	0.79	deleterious	None	None	None	None	N
E/G	0.6083	likely_pathogenic	0.5372	ambiguous	-1.134	Destabilizing	0.477	N	0.633	neutral	D	0.578653203	None	None	N
E/H	0.8421	likely_pathogenic	0.7798	pathogenic	-0.459	Destabilizing	0.985	D	0.627	neutral	None	None	None	None	N
E/I	0.7521	likely_pathogenic	0.7216	pathogenic	0.009	Stabilizing	0.894	D	0.803	deleterious	None	None	None	None	N
E/K	0.5549	ambiguous	0.4402	ambiguous	-0.129	Destabilizing	0.477	N	0.479	neutral	N	0.48097056	None	None	N
E/L	0.7716	likely_pathogenic	0.7284	pathogenic	0.009	Stabilizing	0.894	D	0.757	deleterious	None	None	None	None	N
E/M	0.7606	likely_pathogenic	0.7194	pathogenic	0.352	Stabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
E/N	0.5796	likely_pathogenic	0.5193	ambiguous	-0.65	Destabilizing	0.547	D	0.567	neutral	None	None	None	None	N
E/P	0.92	likely_pathogenic	0.9237	pathogenic	-0.247	Destabilizing	0.945	D	0.783	deleterious	None	None	None	None	N
E/Q	0.3428	ambiguous	0.2781	benign	-0.56	Destabilizing	0.864	D	0.611	neutral	N	0.473009857	None	None	N
E/R	0.7387	likely_pathogenic	0.6504	pathogenic	0.109	Stabilizing	0.894	D	0.651	neutral	None	None	None	None	N
E/S	0.4605	ambiguous	0.4037	ambiguous	-0.884	Destabilizing	0.007	N	0.348	neutral	None	None	None	None	N
E/T	0.5323	ambiguous	0.4779	ambiguous	-0.62	Destabilizing	0.547	D	0.655	neutral	None	None	None	None	N
E/V	0.5154	ambiguous	0.47	ambiguous	-0.247	Destabilizing	0.864	D	0.742	deleterious	N	0.499450818	None	None	N
E/W	0.9845	likely_pathogenic	0.9783	pathogenic	-0.056	Destabilizing	0.995	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.9179	likely_pathogenic	0.8906	pathogenic	-0.072	Destabilizing	0.945	D	0.782	deleterious	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.