TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23324	70195;70196;70197	chr2:178576162;178576161;178576160	chr2:179440889;179440888;179440887
N2AB	21683	65272;65273;65274	chr2:178576162;178576161;178576160	chr2:179440889;179440888;179440887
N2A	20756	62491;62492;62493	chr2:178576162;178576161;178576160	chr2:179440889;179440888;179440887
N2B	14259	43000;43001;43002	chr2:178576162;178576161;178576160	chr2:179440889;179440888;179440887
Novex-1	14384	43375;43376;43377	chr2:178576162;178576161;178576160	chr2:179440889;179440888;179440887
Novex-2	14451	43576;43577;43578	chr2:178576162;178576161;178576160	chr2:179440889;179440888;179440887
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-57
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.4465
• 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
V/A	None	None	None	N	0.25	0.089	0.388174495139	gnomAD-4.0.0	1.36898E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79942E-06	0	0
V/F	None	None	0.171	N	0.625	0.103	0.629781192331	gnomAD-4.0.0	3.18564E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72164E-06	0	0
V/I	rs1710011007	None	None	N	0.234	0.053	0.315903272564	gnomAD-4.0.0	1.59282E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4348E-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
V/A	0.0967	likely_benign	0.093	benign	-0.859	Destabilizing	None	N	0.25	neutral	N	0.446173199	None	None	I
V/C	0.5428	ambiguous	0.4898	ambiguous	-0.749	Destabilizing	0.676	D	0.603	neutral	None	None	None	None	I
V/D	0.3112	likely_benign	0.292	benign	-0.378	Destabilizing	0.029	N	0.642	neutral	N	0.500487687	None	None	I
V/E	0.1973	likely_benign	0.1901	benign	-0.468	Destabilizing	None	N	0.515	neutral	None	None	None	None	I
V/F	0.134	likely_benign	0.1223	benign	-0.9	Destabilizing	0.171	N	0.625	neutral	N	0.497255381	None	None	I
V/G	0.2056	likely_benign	0.1988	benign	-1.049	Destabilizing	0.029	N	0.607	neutral	N	0.519766881	None	None	I
V/H	0.4174	ambiguous	0.3781	ambiguous	-0.509	Destabilizing	0.676	D	0.641	neutral	None	None	None	None	I
V/I	0.0651	likely_benign	0.0638	benign	-0.491	Destabilizing	None	N	0.234	neutral	N	0.468529984	None	None	I
V/K	0.2259	likely_benign	0.2069	benign	-0.612	Destabilizing	0.038	N	0.614	neutral	None	None	None	None	I
V/L	0.1277	likely_benign	0.1142	benign	-0.491	Destabilizing	None	N	0.231	neutral	N	0.433358618	None	None	I
V/M	0.1065	likely_benign	0.102	benign	-0.399	Destabilizing	0.214	N	0.604	neutral	None	None	None	None	I
V/N	0.2239	likely_benign	0.2028	benign	-0.335	Destabilizing	0.214	N	0.641	neutral	None	None	None	None	I
V/P	0.2473	likely_benign	0.2216	benign	-0.577	Destabilizing	0.356	N	0.637	neutral	None	None	None	None	I
V/Q	0.2235	likely_benign	0.2132	benign	-0.596	Destabilizing	0.12	N	0.641	neutral	None	None	None	None	I
V/R	0.2029	likely_benign	0.1835	benign	-0.055	Destabilizing	0.214	N	0.641	neutral	None	None	None	None	I
V/S	0.1508	likely_benign	0.1434	benign	-0.811	Destabilizing	0.038	N	0.584	neutral	None	None	None	None	I
V/T	0.1079	likely_benign	0.0992	benign	-0.795	Destabilizing	0.001	N	0.264	neutral	None	None	None	None	I
V/W	0.6359	likely_pathogenic	0.6035	pathogenic	-0.946	Destabilizing	0.864	D	0.657	neutral	None	None	None	None	I
V/Y	0.4032	ambiguous	0.3689	ambiguous	-0.661	Destabilizing	0.356	N	0.614	neutral	None	None	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.