TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23987	72184;72185;72186	chr2:178574173;178574172;178574171	chr2:179438900;179438899;179438898
N2AB	22346	67261;67262;67263	chr2:178574173;178574172;178574171	chr2:179438900;179438899;179438898
N2A	21419	64480;64481;64482	chr2:178574173;178574172;178574171	chr2:179438900;179438899;179438898
N2B	14922	44989;44990;44991	chr2:178574173;178574172;178574171	chr2:179438900;179438899;179438898
Novex-1	15047	45364;45365;45366	chr2:178574173;178574172;178574171	chr2:179438900;179438899;179438898
Novex-2	15114	45565;45566;45567	chr2:178574173;178574172;178574171	chr2:179438900;179438899;179438898
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: Fn3-62
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4746
• 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/T	rs764752985	-0.298	0.17	N	0.325	0.129	0.110078149338	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	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	0.1018	likely_benign	0.1033	benign	-0.268	Destabilizing	0.807	D	0.349	neutral	None	None	None	None	N
S/C	0.2017	likely_benign	0.2088	benign	-0.302	Destabilizing	0.999	D	0.739	prob.delet.	N	0.474499564	None	None	N
S/D	0.6259	likely_pathogenic	0.6418	pathogenic	0.399	Stabilizing	0.953	D	0.517	neutral	None	None	None	None	N
S/E	0.7262	likely_pathogenic	0.7248	pathogenic	0.308	Stabilizing	0.953	D	0.521	neutral	None	None	None	None	N
S/F	0.3247	likely_benign	0.3396	benign	-0.892	Destabilizing	0.993	D	0.783	deleterious	None	None	None	None	N
S/G	0.1141	likely_benign	0.1183	benign	-0.367	Destabilizing	0.939	D	0.429	neutral	N	0.484158371	None	None	N
S/H	0.5728	likely_pathogenic	0.5741	pathogenic	-0.782	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
S/I	0.2895	likely_benign	0.2938	benign	-0.14	Destabilizing	0.982	D	0.775	deleterious	N	0.507843308	None	None	N
S/K	0.8548	likely_pathogenic	0.8663	pathogenic	-0.312	Destabilizing	0.953	D	0.514	neutral	None	None	None	None	N
S/L	0.1193	likely_benign	0.1216	benign	-0.14	Destabilizing	0.91	D	0.625	neutral	None	None	None	None	N
S/M	0.2501	likely_benign	0.2426	benign	-0.066	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
S/N	0.2123	likely_benign	0.2113	benign	-0.08	Destabilizing	0.939	D	0.507	neutral	N	0.502877418	None	None	N
S/P	0.2405	likely_benign	0.2401	benign	-0.154	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
S/Q	0.702	likely_pathogenic	0.694	pathogenic	-0.285	Destabilizing	0.993	D	0.643	neutral	None	None	None	None	N
S/R	0.8239	likely_pathogenic	0.845	pathogenic	-0.134	Destabilizing	0.991	D	0.779	deleterious	N	0.489852193	None	None	N
S/T	0.0742	likely_benign	0.0742	benign	-0.2	Destabilizing	0.17	N	0.325	neutral	N	0.36908064	None	None	N
S/V	0.2837	likely_benign	0.2815	benign	-0.154	Destabilizing	0.973	D	0.692	prob.neutral	None	None	None	None	N
S/W	0.5296	ambiguous	0.5498	ambiguous	-0.926	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
S/Y	0.3162	likely_benign	0.3292	benign	-0.615	Destabilizing	0.998	D	0.775	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.