TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6015	18268;18269;18270	chr2:178730357;178730356;178730355	chr2:179595084;179595083;179595082
N2AB	5698	17317;17318;17319	chr2:178730357;178730356;178730355	chr2:179595084;179595083;179595082
N2A	4771	14536;14537;14538	chr2:178730357;178730356;178730355	chr2:179595084;179595083;179595082
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-44
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.587
• 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
V/M	rs753892185	-0.235	0.004	N	0.203	0.037	0.141422826196	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.53E-05	None	0	0	0
V/M	rs753892185	-0.235	0.004	N	0.203	0.037	0.141422826196	gnomAD-4.0.0	1.37766E-06	None	None	None	None	N	None	3.01296E-05	0	None	0	0	None	0	0	0	1.1836E-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	0.1544	likely_benign	0.1324	benign	-1.025	Destabilizing	0.027	N	0.276	neutral	N	0.469215057	None	None	N
V/C	0.8	likely_pathogenic	0.7142	pathogenic	-0.674	Destabilizing	0.935	D	0.336	neutral	None	None	None	None	N
V/D	0.4144	ambiguous	0.3666	ambiguous	-0.596	Destabilizing	0.555	D	0.424	neutral	None	None	None	None	N
V/E	0.2396	likely_benign	0.2054	benign	-0.592	Destabilizing	0.484	N	0.416	neutral	N	0.478354615	None	None	N
V/F	0.1852	likely_benign	0.1534	benign	-0.711	Destabilizing	0.235	N	0.387	neutral	None	None	None	None	N
V/G	0.2731	likely_benign	0.2386	benign	-1.307	Destabilizing	0.484	N	0.413	neutral	N	0.460162339	None	None	N
V/H	0.4918	ambiguous	0.4281	ambiguous	-0.644	Destabilizing	0.935	D	0.393	neutral	None	None	None	None	N
V/I	0.0705	likely_benign	0.0707	benign	-0.365	Destabilizing	None	N	0.083	neutral	None	None	None	None	N
V/K	0.2434	likely_benign	0.204	benign	-0.818	Destabilizing	0.38	N	0.407	neutral	None	None	None	None	N
V/L	0.1266	likely_benign	0.1017	benign	-0.365	Destabilizing	None	N	0.059	neutral	N	0.412860341	None	None	N
V/M	0.1231	likely_benign	0.1093	benign	-0.379	Destabilizing	0.004	N	0.203	neutral	N	0.498460528	None	None	N
V/N	0.3367	likely_benign	0.2994	benign	-0.715	Destabilizing	0.555	D	0.405	neutral	None	None	None	None	N
V/P	0.7152	likely_pathogenic	0.6168	pathogenic	-0.55	Destabilizing	0.791	D	0.41	neutral	None	None	None	None	N
V/Q	0.2264	likely_benign	0.1885	benign	-0.834	Destabilizing	0.38	N	0.391	neutral	None	None	None	None	N
V/R	0.2066	likely_benign	0.1617	benign	-0.322	Destabilizing	0.38	N	0.417	neutral	None	None	None	None	N
V/S	0.2017	likely_benign	0.1787	benign	-1.225	Destabilizing	0.149	N	0.397	neutral	None	None	None	None	N
V/T	0.1257	likely_benign	0.1189	benign	-1.108	Destabilizing	0.149	N	0.282	neutral	None	None	None	None	N
V/W	0.699	likely_pathogenic	0.6044	pathogenic	-0.892	Destabilizing	0.935	D	0.448	neutral	None	None	None	None	N
V/Y	0.538	ambiguous	0.4562	ambiguous	-0.576	Destabilizing	0.555	D	0.369	neutral	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.