TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8584	25975;25976;25977	chr2:178715664;178715663;178715662	chr2:179580391;179580390;179580389
N2AB	8267	25024;25025;25026	chr2:178715664;178715663;178715662	chr2:179580391;179580390;179580389
N2A	7340	22243;22244;22245	chr2:178715664;178715663;178715662	chr2:179580391;179580390;179580389
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-71
• Domain position: 36
• Structural Position: 49
• Q(SASA): 0.1548
• 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/C	rs1440957407	None	0.999	N	0.674	0.315	0.475741759771	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
Y/C	rs1440957407	None	0.999	N	0.674	0.315	0.475741759771	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
Y/C	rs1440957407	None	0.999	N	0.674	0.315	0.475741759771	gnomAD-4.0.0	1.3146E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94066E-05	0	0
Y/H	None	None	0.989	N	0.667	0.361	0.350964488264	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.869	likely_pathogenic	0.8482	pathogenic	-2.944	Highly Destabilizing	0.973	D	0.605	neutral	None	None	None	None	N
Y/C	0.3932	ambiguous	0.3667	ambiguous	-1.536	Destabilizing	0.999	D	0.674	neutral	N	0.52063085	None	None	N
Y/D	0.8218	likely_pathogenic	0.8043	pathogenic	-2.189	Highly Destabilizing	0.997	D	0.724	prob.delet.	N	0.520377361	None	None	N
Y/E	0.8789	likely_pathogenic	0.8608	pathogenic	-2.082	Highly Destabilizing	0.997	D	0.656	neutral	None	None	None	None	N
Y/F	0.0803	likely_benign	0.0758	benign	-1.266	Destabilizing	0.005	N	0.245	neutral	N	0.438372075	None	None	N
Y/G	0.7864	likely_pathogenic	0.7605	pathogenic	-3.281	Highly Destabilizing	0.992	D	0.691	prob.neutral	None	None	None	None	N
Y/H	0.2896	likely_benign	0.2662	benign	-1.591	Destabilizing	0.989	D	0.667	neutral	N	0.484079945	None	None	N
Y/I	0.6644	likely_pathogenic	0.6478	pathogenic	-1.877	Destabilizing	0.551	D	0.641	neutral	None	None	None	None	N
Y/K	0.6931	likely_pathogenic	0.6577	pathogenic	-1.625	Destabilizing	0.979	D	0.656	neutral	None	None	None	None	N
Y/L	0.5866	likely_pathogenic	0.5596	ambiguous	-1.877	Destabilizing	0.259	N	0.514	neutral	None	None	None	None	N
Y/M	0.6842	likely_pathogenic	0.6554	pathogenic	-1.562	Destabilizing	0.993	D	0.674	neutral	None	None	None	None	N
Y/N	0.472	ambiguous	0.4436	ambiguous	-1.965	Destabilizing	0.997	D	0.688	prob.neutral	N	0.482523009	None	None	N
Y/P	0.9954	likely_pathogenic	0.9947	pathogenic	-2.235	Highly Destabilizing	0.997	D	0.728	prob.delet.	None	None	None	None	N
Y/Q	0.6972	likely_pathogenic	0.6638	pathogenic	-1.959	Destabilizing	0.992	D	0.683	prob.neutral	None	None	None	None	N
Y/R	0.5614	ambiguous	0.5269	ambiguous	-1.055	Destabilizing	0.994	D	0.689	prob.neutral	None	None	None	None	N
Y/S	0.6142	likely_pathogenic	0.581	pathogenic	-2.486	Highly Destabilizing	0.99	D	0.651	neutral	N	0.466936742	None	None	N
Y/T	0.7689	likely_pathogenic	0.7407	pathogenic	-2.281	Highly Destabilizing	0.992	D	0.655	neutral	None	None	None	None	N
Y/V	0.6036	likely_pathogenic	0.5928	pathogenic	-2.235	Highly Destabilizing	0.948	D	0.593	neutral	None	None	None	None	N
Y/W	0.4497	ambiguous	0.4362	ambiguous	-0.675	Destabilizing	0.999	D	0.659	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.