TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18389	55390;55391;55392	chr2:178602106;178602105;178602104	chr2:179466833;179466832;179466831
N2AB	16748	50467;50468;50469	chr2:178602106;178602105;178602104	chr2:179466833;179466832;179466831
N2A	15821	47686;47687;47688	chr2:178602106;178602105;178602104	chr2:179466833;179466832;179466831
N2B	9324	28195;28196;28197	chr2:178602106;178602105;178602104	chr2:179466833;179466832;179466831
Novex-1	9449	28570;28571;28572	chr2:178602106;178602105;178602104	chr2:179466833;179466832;179466831
Novex-2	9516	28771;28772;28773	chr2:178602106;178602105;178602104	chr2:179466833;179466832;179466831
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: Ig-115
• Domain position: 8
• Structural Position: 14
• Q(SASA): 0.459
• 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/L	None	None	None	N	0.131	0.168	0.115124310173	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.1931	likely_benign	0.1915	benign	-0.736	Destabilizing	0.005	N	0.252	neutral	N	0.471933728	None	None	I
V/C	0.5745	likely_pathogenic	0.5505	ambiguous	-0.528	Destabilizing	None	N	0.189	neutral	None	None	None	None	I
V/D	0.3654	ambiguous	0.4163	ambiguous	-0.728	Destabilizing	0.029	N	0.471	neutral	N	0.48401759	None	None	I
V/E	0.2873	likely_benign	0.3323	benign	-0.825	Destabilizing	0.072	N	0.479	neutral	None	None	None	None	I
V/F	0.1487	likely_benign	0.1516	benign	-0.83	Destabilizing	0.055	N	0.553	neutral	D	0.522151904	None	None	I
V/G	0.2587	likely_benign	0.2722	benign	-0.92	Destabilizing	None	N	0.327	neutral	N	0.521805187	None	None	I
V/H	0.451	ambiguous	0.4656	ambiguous	-0.511	Destabilizing	0.356	N	0.442	neutral	None	None	None	None	I
V/I	0.0727	likely_benign	0.0646	benign	-0.383	Destabilizing	None	N	0.081	neutral	N	0.436149073	None	None	I
V/K	0.3985	ambiguous	0.4526	ambiguous	-0.734	Destabilizing	0.072	N	0.483	neutral	None	None	None	None	I
V/L	0.1477	likely_benign	0.1279	benign	-0.383	Destabilizing	None	N	0.131	neutral	N	0.465605188	None	None	I
V/M	0.1593	likely_benign	0.1368	benign	-0.308	Destabilizing	0.214	N	0.447	neutral	None	None	None	None	I
V/N	0.2049	likely_benign	0.1939	benign	-0.372	Destabilizing	None	N	0.338	neutral	None	None	None	None	I
V/P	0.5841	likely_pathogenic	0.5906	pathogenic	-0.466	Destabilizing	0.136	N	0.559	neutral	None	None	None	None	I
V/Q	0.2768	likely_benign	0.3038	benign	-0.634	Destabilizing	0.356	N	0.575	neutral	None	None	None	None	I
V/R	0.3493	ambiguous	0.4036	ambiguous	-0.153	Destabilizing	0.072	N	0.549	neutral	None	None	None	None	I
V/S	0.1678	likely_benign	0.1664	benign	-0.717	Destabilizing	None	N	0.27	neutral	None	None	None	None	I
V/T	0.1444	likely_benign	0.1398	benign	-0.718	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
V/W	0.7074	likely_pathogenic	0.7293	pathogenic	-0.94	Destabilizing	0.864	D	0.462	neutral	None	None	None	None	I
V/Y	0.4221	ambiguous	0.4213	ambiguous	-0.657	Destabilizing	0.356	N	0.568	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.