TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6679	20260;20261;20262	chr2:178727330;178727329;178727328	chr2:179592057;179592056;179592055
N2AB	6362	19309;19310;19311	chr2:178727330;178727329;178727328	chr2:179592057;179592056;179592055
N2A	5435	16528;16529;16530	chr2:178727330;178727329;178727328	chr2:179592057;179592056;179592055
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-51
• Domain position: 13
• Structural Position: 17
• Q(SASA): 0.2334
• 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/E	None	None	0.669	D	0.569	0.653	0.857261922848	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
V/L	None	None	0.008	N	0.394	0.179	0.552492811922	gnomAD-4.0.0	6.86256E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0137E-07	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
V/A	0.2929	likely_benign	0.3027	benign	-1.767	Destabilizing	0.263	N	0.443	neutral	D	0.53379305	None	None	N
V/C	0.7985	likely_pathogenic	0.8275	pathogenic	-1.338	Destabilizing	0.987	D	0.514	neutral	None	None	None	None	N
V/D	0.8569	likely_pathogenic	0.884	pathogenic	-1.726	Destabilizing	0.943	D	0.619	neutral	None	None	None	None	N
V/E	0.6713	likely_pathogenic	0.6995	pathogenic	-1.651	Destabilizing	0.669	D	0.569	neutral	D	0.52448323	None	None	N
V/F	0.218	likely_benign	0.278	benign	-1.159	Destabilizing	0.86	D	0.553	neutral	None	None	None	None	N
V/G	0.4755	ambiguous	0.4681	ambiguous	-2.166	Highly Destabilizing	0.944	D	0.614	neutral	N	0.51583595	None	None	N
V/H	0.8167	likely_pathogenic	0.8615	pathogenic	-1.71	Destabilizing	0.99	D	0.587	neutral	None	None	None	None	N
V/I	0.0797	likely_benign	0.086	benign	-0.734	Destabilizing	None	N	0.236	neutral	None	None	None	None	N
V/K	0.7394	likely_pathogenic	0.7771	pathogenic	-1.571	Destabilizing	0.742	D	0.561	neutral	None	None	None	None	N
V/L	0.1632	likely_benign	0.2376	benign	-0.734	Destabilizing	0.008	N	0.394	neutral	N	0.51299649	None	None	N
V/M	0.167	likely_benign	0.2021	benign	-0.669	Destabilizing	0.063	N	0.421	neutral	N	0.521507489	None	None	N
V/N	0.7164	likely_pathogenic	0.7537	pathogenic	-1.512	Destabilizing	0.464	N	0.625	neutral	None	None	None	None	N
V/P	0.9565	likely_pathogenic	0.9638	pathogenic	-1.046	Destabilizing	0.725	D	0.562	neutral	None	None	None	None	N
V/Q	0.5853	likely_pathogenic	0.6246	pathogenic	-1.576	Destabilizing	0.805	D	0.567	neutral	None	None	None	None	N
V/R	0.6583	likely_pathogenic	0.7126	pathogenic	-1.133	Destabilizing	0.86	D	0.625	neutral	None	None	None	None	N
V/S	0.4724	ambiguous	0.4865	ambiguous	-2.11	Highly Destabilizing	0.768	D	0.557	neutral	None	None	None	None	N
V/T	0.3518	ambiguous	0.3583	ambiguous	-1.916	Destabilizing	0.276	N	0.535	neutral	None	None	None	None	N
V/W	0.8853	likely_pathogenic	0.92	pathogenic	-1.445	Destabilizing	0.997	D	0.554	neutral	None	None	None	None	N
V/Y	0.6912	likely_pathogenic	0.7678	pathogenic	-1.137	Destabilizing	0.926	D	0.541	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.