TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19430	58513;58514;58515	chr2:178594105;178594104;178594103	chr2:179458832;179458831;179458830
N2AB	17789	53590;53591;53592	chr2:178594105;178594104;178594103	chr2:179458832;179458831;179458830
N2A	16862	50809;50810;50811	chr2:178594105;178594104;178594103	chr2:179458832;179458831;179458830
N2B	10365	31318;31319;31320	chr2:178594105;178594104;178594103	chr2:179458832;179458831;179458830
Novex-1	10490	31693;31694;31695	chr2:178594105;178594104;178594103	chr2:179458832;179458831;179458830
Novex-2	10557	31894;31895;31896	chr2:178594105;178594104;178594103	chr2:179458832;179458831;179458830
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-118
• Domain position: 40
• Structural Position: 73
• Q(SASA): 0.306
• 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
D/N	None	None	0.322	N	0.263	0.112	0.17948927462	gnomAD-4.0.0	1.59201E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	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
D/A	0.5017	ambiguous	0.4513	ambiguous	-0.216	Destabilizing	0.885	D	0.487	neutral	N	0.461985991	None	None	N
D/C	0.7982	likely_pathogenic	0.7618	pathogenic	0.149	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
D/E	0.5415	ambiguous	0.5104	ambiguous	-0.313	Destabilizing	0.939	D	0.411	neutral	N	0.461225523	None	None	N
D/F	0.9083	likely_pathogenic	0.8831	pathogenic	-0.415	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
D/G	0.2698	likely_benign	0.239	benign	-0.424	Destabilizing	0.885	D	0.442	neutral	N	0.476909033	None	None	N
D/H	0.717	likely_pathogenic	0.664	pathogenic	-0.585	Destabilizing	0.998	D	0.537	neutral	N	0.471963171	None	None	N
D/I	0.8189	likely_pathogenic	0.7847	pathogenic	0.285	Stabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
D/K	0.781	likely_pathogenic	0.73	pathogenic	-0.08	Destabilizing	0.986	D	0.507	neutral	None	None	None	None	N
D/L	0.7675	likely_pathogenic	0.7251	pathogenic	0.285	Stabilizing	0.986	D	0.683	prob.neutral	None	None	None	None	N
D/M	0.8633	likely_pathogenic	0.832	pathogenic	0.591	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
D/N	0.1572	likely_benign	0.1461	benign	-0.071	Destabilizing	0.322	N	0.263	neutral	N	0.471543286	None	None	N
D/P	0.9291	likely_pathogenic	0.9149	pathogenic	0.141	Stabilizing	0.993	D	0.535	neutral	None	None	None	None	N
D/Q	0.7967	likely_pathogenic	0.7572	pathogenic	-0.038	Destabilizing	0.993	D	0.5	neutral	None	None	None	None	N
D/R	0.8351	likely_pathogenic	0.7841	pathogenic	-0.019	Destabilizing	0.986	D	0.625	neutral	None	None	None	None	N
D/S	0.272	likely_benign	0.2441	benign	-0.252	Destabilizing	0.386	N	0.269	neutral	None	None	None	None	N
D/T	0.402	ambiguous	0.3605	ambiguous	-0.111	Destabilizing	0.91	D	0.47	neutral	None	None	None	None	N
D/V	0.591	likely_pathogenic	0.5468	ambiguous	0.141	Stabilizing	0.982	D	0.69	prob.neutral	N	0.468684715	None	None	N
D/W	0.9736	likely_pathogenic	0.9624	pathogenic	-0.428	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
D/Y	0.6354	likely_pathogenic	0.5586	ambiguous	-0.247	Destabilizing	0.999	D	0.674	neutral	N	0.477078506	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.