TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23265	70018;70019;70020	chr2:178576339;178576338;178576337	chr2:179441066;179441065;179441064
N2AB	21624	65095;65096;65097	chr2:178576339;178576338;178576337	chr2:179441066;179441065;179441064
N2A	20697	62314;62315;62316	chr2:178576339;178576338;178576337	chr2:179441066;179441065;179441064
N2B	14200	42823;42824;42825	chr2:178576339;178576338;178576337	chr2:179441066;179441065;179441064
Novex-1	14325	43198;43199;43200	chr2:178576339;178576338;178576337	chr2:179441066;179441065;179441064
Novex-2	14392	43399;43400;43401	chr2:178576339;178576338;178576337	chr2:179441066;179441065;179441064
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-57
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.1392
• Predicted PPI site: I

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
H/Y	rs1265649343	0.929	0.521	N	0.397	0.26	0.197625483188	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
H/Y	rs1265649343	0.929	0.521	N	0.397	0.26	0.197625483188	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/Y	rs1265649343	0.929	0.521	N	0.397	0.26	0.197625483188	gnomAD-4.0.0	6.57626E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47076E-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
H/A	0.3213	likely_benign	0.3871	ambiguous	0.362	Stabilizing	0.373	N	0.367	neutral	None	None	None	None	I
H/C	0.2601	likely_benign	0.2551	benign	0.522	Stabilizing	0.996	D	0.351	neutral	None	None	None	None	I
H/D	0.4878	ambiguous	0.5811	pathogenic	-0.05	Destabilizing	0.684	D	0.42	neutral	N	0.353284468	None	None	I
H/E	0.5541	ambiguous	0.6415	pathogenic	-0.052	Destabilizing	0.742	D	0.366	neutral	None	None	None	None	I
H/F	0.288	likely_benign	0.2933	benign	0.82	Stabilizing	0.009	N	0.257	neutral	None	None	None	None	I
H/G	0.4669	ambiguous	0.5427	ambiguous	0.146	Stabilizing	0.742	D	0.447	neutral	None	None	None	None	I
H/I	0.2585	likely_benign	0.3117	benign	0.885	Stabilizing	0.91	D	0.399	neutral	None	None	None	None	I
H/K	0.4547	ambiguous	0.5211	ambiguous	0.281	Stabilizing	0.59	D	0.433	neutral	None	None	None	None	I
H/L	0.121	likely_benign	0.1456	benign	0.885	Stabilizing	0.521	D	0.461	neutral	N	0.343299548	None	None	I
H/M	0.4355	ambiguous	0.4906	ambiguous	0.613	Stabilizing	0.984	D	0.375	neutral	None	None	None	None	I
H/N	0.1595	likely_benign	0.2093	benign	0.22	Stabilizing	0.684	D	0.404	neutral	N	0.431014533	None	None	I
H/P	0.2429	likely_benign	0.2947	benign	0.734	Stabilizing	0.939	D	0.423	neutral	N	0.391360067	None	None	I
H/Q	0.2876	likely_benign	0.3577	ambiguous	0.265	Stabilizing	0.884	D	0.349	neutral	N	0.405156083	None	None	I
H/R	0.2025	likely_benign	0.241	benign	-0.143	Destabilizing	0.007	N	0.225	neutral	N	0.388935837	None	None	I
H/S	0.2842	likely_benign	0.3569	ambiguous	0.286	Stabilizing	0.101	N	0.251	neutral	None	None	None	None	I
H/T	0.3743	ambiguous	0.4431	ambiguous	0.376	Stabilizing	0.59	D	0.455	neutral	None	None	None	None	I
H/V	0.2271	likely_benign	0.2757	benign	0.734	Stabilizing	0.742	D	0.421	neutral	None	None	None	None	I
H/W	0.4752	ambiguous	0.4629	ambiguous	0.724	Stabilizing	0.996	D	0.381	neutral	None	None	None	None	I
H/Y	0.1097	likely_benign	0.1211	benign	1.015	Stabilizing	0.521	D	0.397	neutral	N	0.437633861	None	None	I

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.