TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15989	48190;48191;48192	chr2:178616924;178616923;178616922	chr2:179481651;179481650;179481649
N2AB	14348	43267;43268;43269	chr2:178616924;178616923;178616922	chr2:179481651;179481650;179481649
N2A	13421	40486;40487;40488	chr2:178616924;178616923;178616922	chr2:179481651;179481650;179481649
N2B	6924	20995;20996;20997	chr2:178616924;178616923;178616922	chr2:179481651;179481650;179481649
Novex-1	7049	21370;21371;21372	chr2:178616924;178616923;178616922	chr2:179481651;179481650;179481649
Novex-2	7116	21571;21572;21573	chr2:178616924;178616923;178616922	chr2:179481651;179481650;179481649
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: Ig-109
• Domain position: 22
• Structural Position: 41
• Q(SASA): 0.7214
• 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
Y/S	rs2057440561	None	1.0	D	0.686	0.577	0.784478220262	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
Y/S	rs2057440561	None	1.0	D	0.686	0.577	0.784478220262	gnomAD-4.0.0	2.48052E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.39252E-05	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	0.8034	likely_pathogenic	0.7662	pathogenic	-0.32	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
Y/C	0.4167	ambiguous	0.3506	ambiguous	0.062	Stabilizing	1.0	D	0.739	prob.delet.	D	0.579631142	None	None	I
Y/D	0.7279	likely_pathogenic	0.6886	pathogenic	0.606	Stabilizing	1.0	D	0.706	prob.neutral	N	0.499264053	None	None	I
Y/E	0.8942	likely_pathogenic	0.8512	pathogenic	0.572	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
Y/F	0.1349	likely_benign	0.1194	benign	-0.291	Destabilizing	0.999	D	0.559	neutral	N	0.508086517	None	None	I
Y/G	0.8349	likely_pathogenic	0.8101	pathogenic	-0.448	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
Y/H	0.3731	ambiguous	0.321	benign	0.329	Stabilizing	1.0	D	0.701	prob.neutral	D	0.579482874	None	None	I
Y/I	0.6083	likely_pathogenic	0.5678	pathogenic	-0.028	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
Y/K	0.7563	likely_pathogenic	0.6821	pathogenic	0.208	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
Y/L	0.6643	likely_pathogenic	0.6157	pathogenic	-0.028	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
Y/M	0.7951	likely_pathogenic	0.7477	pathogenic	-0.134	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
Y/N	0.3832	ambiguous	0.3502	ambiguous	-0.066	Destabilizing	1.0	D	0.71	prob.delet.	N	0.499264053	None	None	I
Y/P	0.9726	likely_pathogenic	0.9648	pathogenic	-0.107	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
Y/Q	0.792	likely_pathogenic	0.7191	pathogenic	0.011	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
Y/R	0.6393	likely_pathogenic	0.5601	ambiguous	0.329	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
Y/S	0.406	ambiguous	0.3851	ambiguous	-0.335	Destabilizing	1.0	D	0.686	prob.neutral	D	0.573787355	None	None	I
Y/T	0.7649	likely_pathogenic	0.7023	pathogenic	-0.287	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
Y/V	0.5715	likely_pathogenic	0.5177	ambiguous	-0.107	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
Y/W	0.6046	likely_pathogenic	0.5685	pathogenic	-0.564	Destabilizing	1.0	D	0.7	prob.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.