TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20694	62305;62306;62307	chr2:178589645;178589644;178589643	chr2:179454372;179454371;179454370
N2AB	19053	57382;57383;57384	chr2:178589645;178589644;178589643	chr2:179454372;179454371;179454370
N2A	18126	54601;54602;54603	chr2:178589645;178589644;178589643	chr2:179454372;179454371;179454370
N2B	11629	35110;35111;35112	chr2:178589645;178589644;178589643	chr2:179454372;179454371;179454370
Novex-1	11754	35485;35486;35487	chr2:178589645;178589644;178589643	chr2:179454372;179454371;179454370
Novex-2	11821	35686;35687;35688	chr2:178589645;178589644;178589643	chr2:179454372;179454371;179454370
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-38
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5099
• 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
Y/S	None	None	1.0	N	0.645	0.347	0.545346552841	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
Y/A	0.9045	likely_pathogenic	0.8069	pathogenic	-0.737	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
Y/C	0.6242	likely_pathogenic	0.3557	ambiguous	0.11	Stabilizing	1.0	D	0.678	prob.neutral	N	0.478580352	None	None	N
Y/D	0.753	likely_pathogenic	0.5428	ambiguous	1.02	Stabilizing	1.0	D	0.693	prob.neutral	N	0.467873836	None	None	N
Y/E	0.9473	likely_pathogenic	0.8785	pathogenic	0.999	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
Y/F	0.1762	likely_benign	0.1338	benign	-0.386	Destabilizing	0.434	N	0.283	neutral	N	0.482189928	None	None	N
Y/G	0.8257	likely_pathogenic	0.7514	pathogenic	-0.922	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
Y/H	0.5572	ambiguous	0.3806	ambiguous	0.171	Stabilizing	1.0	D	0.653	neutral	N	0.508413737	None	None	N
Y/I	0.9027	likely_pathogenic	0.7757	pathogenic	-0.276	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
Y/K	0.9301	likely_pathogenic	0.8604	pathogenic	0.224	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
Y/L	0.8689	likely_pathogenic	0.7821	pathogenic	-0.276	Destabilizing	0.994	D	0.556	neutral	None	None	None	None	N
Y/M	0.9105	likely_pathogenic	0.8313	pathogenic	-0.065	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
Y/N	0.4039	ambiguous	0.2626	benign	0.073	Stabilizing	1.0	D	0.673	neutral	N	0.451963021	None	None	N
Y/P	0.9947	likely_pathogenic	0.9895	pathogenic	-0.41	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
Y/Q	0.9203	likely_pathogenic	0.832	pathogenic	0.094	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
Y/R	0.8228	likely_pathogenic	0.7253	pathogenic	0.507	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
Y/S	0.5512	ambiguous	0.3899	ambiguous	-0.406	Destabilizing	1.0	D	0.645	neutral	N	0.468585912	None	None	N
Y/T	0.8256	likely_pathogenic	0.6629	pathogenic	-0.337	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
Y/V	0.8278	likely_pathogenic	0.6699	pathogenic	-0.41	Destabilizing	0.997	D	0.568	neutral	None	None	None	None	N
Y/W	0.6519	likely_pathogenic	0.5856	pathogenic	-0.48	Destabilizing	1.0	D	0.634	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.