TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15403	46432;46433;46434	chr2:178620314;178620313;178620312	chr2:179485041;179485040;179485039
N2AB	13762	41509;41510;41511	chr2:178620314;178620313;178620312	chr2:179485041;179485040;179485039
N2A	12835	38728;38729;38730	chr2:178620314;178620313;178620312	chr2:179485041;179485040;179485039
N2B	6338	19237;19238;19239	chr2:178620314;178620313;178620312	chr2:179485041;179485040;179485039
Novex-1	6463	19612;19613;19614	chr2:178620314;178620313;178620312	chr2:179485041;179485040;179485039
Novex-2	6530	19813;19814;19815	chr2:178620314;178620313;178620312	chr2:179485041;179485040;179485039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-106
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.3706
• 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
T/S	None	None	0.969	N	0.542	0.259	0.464098490096	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
T/A	0.1382	likely_benign	0.1249	benign	-0.302	Destabilizing	0.863	D	0.516	neutral	N	0.487936459	None	None	N
T/C	0.6394	likely_pathogenic	0.6481	pathogenic	-0.238	Destabilizing	0.999	D	0.549	neutral	None	None	None	None	N
T/D	0.6858	likely_pathogenic	0.6697	pathogenic	0.074	Stabilizing	0.998	D	0.531	neutral	None	None	None	None	N
T/E	0.4755	ambiguous	0.4615	ambiguous	-0.007	Destabilizing	0.998	D	0.51	neutral	None	None	None	None	N
T/F	0.4808	ambiguous	0.4711	ambiguous	-0.803	Destabilizing	0.986	D	0.665	neutral	None	None	None	None	N
T/G	0.4598	ambiguous	0.45	ambiguous	-0.423	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
T/H	0.4893	ambiguous	0.4877	ambiguous	-0.667	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
T/I	0.2827	likely_benign	0.2718	benign	-0.105	Destabilizing	0.1	N	0.362	neutral	N	0.501193392	None	None	N
T/K	0.2628	likely_benign	0.2547	benign	-0.383	Destabilizing	0.993	D	0.521	neutral	None	None	None	None	N
T/L	0.1521	likely_benign	0.1431	benign	-0.105	Destabilizing	0.807	D	0.512	neutral	None	None	None	None	N
T/M	0.1264	likely_benign	0.1166	benign	None	Stabilizing	0.986	D	0.528	neutral	None	None	None	None	N
T/N	0.2405	likely_benign	0.2276	benign	-0.123	Destabilizing	0.997	D	0.494	neutral	N	0.508584623	None	None	N
T/P	0.325	likely_benign	0.2494	benign	-0.142	Destabilizing	0.997	D	0.514	neutral	N	0.511684454	None	None	N
T/Q	0.3169	likely_benign	0.3112	benign	-0.356	Destabilizing	0.998	D	0.528	neutral	None	None	None	None	N
T/R	0.2238	likely_benign	0.2217	benign	-0.072	Destabilizing	0.998	D	0.514	neutral	None	None	None	None	N
T/S	0.2162	likely_benign	0.1981	benign	-0.311	Destabilizing	0.969	D	0.542	neutral	N	0.497373669	None	None	N
T/V	0.2037	likely_benign	0.2034	benign	-0.142	Destabilizing	0.214	N	0.351	neutral	None	None	None	None	N
T/W	0.8114	likely_pathogenic	0.8041	pathogenic	-0.833	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
T/Y	0.573	likely_pathogenic	0.5679	pathogenic	-0.548	Destabilizing	0.998	D	0.672	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.