TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28727	86404;86405;86406	chr2:178559953;178559952;178559951	chr2:179424680;179424679;179424678
N2AB	27086	81481;81482;81483	chr2:178559953;178559952;178559951	chr2:179424680;179424679;179424678
N2A	26159	78700;78701;78702	chr2:178559953;178559952;178559951	chr2:179424680;179424679;179424678
N2B	19662	59209;59210;59211	chr2:178559953;178559952;178559951	chr2:179424680;179424679;179424678
Novex-1	19787	59584;59585;59586	chr2:178559953;178559952;178559951	chr2:179424680;179424679;179424678
Novex-2	19854	59785;59786;59787	chr2:178559953;178559952;178559951	chr2:179424680;179424679;179424678
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-97
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.0651
• 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/F	rs768069914	-1.971	0.97	N	0.851	0.468	0.641611064703	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
S/F	rs768069914	-1.971	0.97	N	0.851	0.468	0.641611064703	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
S/A	0.0651	likely_benign	0.0661	benign	-2.073	Highly Destabilizing	0.014	N	0.331	neutral	N	0.330008806	None	None	N
S/C	0.185	likely_benign	0.1535	benign	-1.798	Destabilizing	0.032	N	0.605	neutral	N	0.488078537	None	None	N
S/D	0.9934	likely_pathogenic	0.9921	pathogenic	-2.647	Highly Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
S/E	0.9955	likely_pathogenic	0.9948	pathogenic	-2.437	Highly Destabilizing	0.86	D	0.7	prob.neutral	None	None	None	None	N
S/F	0.9791	likely_pathogenic	0.9742	pathogenic	-1.633	Destabilizing	0.97	D	0.851	deleterious	N	0.491204105	None	None	N
S/G	0.2227	likely_benign	0.2236	benign	-2.349	Highly Destabilizing	0.754	D	0.615	neutral	None	None	None	None	N
S/H	0.9912	likely_pathogenic	0.9893	pathogenic	-2.056	Highly Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
S/I	0.8801	likely_pathogenic	0.8424	pathogenic	-1.349	Destabilizing	0.956	D	0.843	deleterious	None	None	None	None	N
S/K	0.9993	likely_pathogenic	0.9993	pathogenic	-1.197	Destabilizing	0.86	D	0.699	prob.neutral	None	None	None	None	N
S/L	0.7134	likely_pathogenic	0.6677	pathogenic	-1.349	Destabilizing	0.754	D	0.827	deleterious	None	None	None	None	N
S/M	0.858	likely_pathogenic	0.8404	pathogenic	-1.606	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
S/N	0.9188	likely_pathogenic	0.9108	pathogenic	-1.818	Destabilizing	0.978	D	0.705	prob.neutral	None	None	None	None	N
S/P	0.9208	likely_pathogenic	0.9512	pathogenic	-1.57	Destabilizing	0.97	D	0.81	deleterious	N	0.467819931	None	None	N
S/Q	0.9923	likely_pathogenic	0.9917	pathogenic	-1.59	Destabilizing	0.978	D	0.698	prob.neutral	None	None	None	None	N
S/R	0.9981	likely_pathogenic	0.998	pathogenic	-1.281	Destabilizing	0.978	D	0.807	deleterious	None	None	None	None	N
S/T	0.3553	ambiguous	0.3298	benign	-1.567	Destabilizing	0.822	D	0.626	neutral	N	0.463438612	None	None	N
S/V	0.7308	likely_pathogenic	0.6847	pathogenic	-1.57	Destabilizing	0.754	D	0.84	deleterious	None	None	None	None	N
S/W	0.9909	likely_pathogenic	0.9899	pathogenic	-1.821	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
S/Y	0.974	likely_pathogenic	0.9637	pathogenic	-1.558	Destabilizing	0.99	D	0.862	deleterious	N	0.491204105	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.