TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22912	68959;68960;68961	chr2:178577692;178577691;178577690	chr2:179442419;179442418;179442417
N2AB	21271	64036;64037;64038	chr2:178577692;178577691;178577690	chr2:179442419;179442418;179442417
N2A	20344	61255;61256;61257	chr2:178577692;178577691;178577690	chr2:179442419;179442418;179442417
N2B	13847	41764;41765;41766	chr2:178577692;178577691;178577690	chr2:179442419;179442418;179442417
Novex-1	13972	42139;42140;42141	chr2:178577692;178577691;178577690	chr2:179442419;179442418;179442417
Novex-2	14039	42340;42341;42342	chr2:178577692;178577691;178577690	chr2:179442419;179442418;179442417
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: Fn3-54
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1458
• 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	rs757919433	-1.744	0.241	D	0.725	0.699	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65412E-04	0	None	0	0	None	0	None	0	0	0
Y/C	rs757919433	-1.744	0.241	D	0.725	0.699	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20616E-04	0	0	0	0	None	0	0	0	0	0
Y/C	rs757919433	-1.744	0.241	D	0.725	0.699	None	gnomAD-4.0.0	7.69114E-06	None	None	None	None	N	None	1.01488E-04	0	None	0	0	None	0	0	0	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	0.9709	likely_pathogenic	0.9642	pathogenic	-3.179	Highly Destabilizing	0.983	D	0.812	deleterious	None	None	None	None	N
Y/C	0.728	likely_pathogenic	0.7237	pathogenic	-1.886	Destabilizing	0.241	N	0.725	prob.delet.	D	0.650183759	None	None	N
Y/D	0.9845	likely_pathogenic	0.9833	pathogenic	-3.62	Highly Destabilizing	0.999	D	0.849	deleterious	D	0.698474006	None	None	N
Y/E	0.9929	likely_pathogenic	0.992	pathogenic	-3.407	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
Y/F	0.2085	likely_benign	0.2391	benign	-1.217	Destabilizing	0.996	D	0.733	prob.delet.	D	0.639080934	None	None	N
Y/G	0.9538	likely_pathogenic	0.9469	pathogenic	-3.602	Highly Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
Y/H	0.8836	likely_pathogenic	0.8721	pathogenic	-2.241	Highly Destabilizing	0.999	D	0.765	deleterious	D	0.682454645	None	None	N
Y/I	0.9155	likely_pathogenic	0.9226	pathogenic	-1.767	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
Y/K	0.9927	likely_pathogenic	0.9923	pathogenic	-2.488	Highly Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
Y/L	0.9176	likely_pathogenic	0.9159	pathogenic	-1.767	Destabilizing	0.983	D	0.774	deleterious	None	None	None	None	N
Y/M	0.9349	likely_pathogenic	0.9315	pathogenic	-1.453	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
Y/N	0.8983	likely_pathogenic	0.8735	pathogenic	-3.341	Highly Destabilizing	0.999	D	0.832	deleterious	D	0.698272202	None	None	N
Y/P	0.9981	likely_pathogenic	0.9984	pathogenic	-2.254	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
Y/Q	0.9828	likely_pathogenic	0.9799	pathogenic	-3.056	Highly Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
Y/R	0.98	likely_pathogenic	0.9791	pathogenic	-2.26	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
Y/S	0.9284	likely_pathogenic	0.9077	pathogenic	-3.654	Highly Destabilizing	0.997	D	0.822	deleterious	D	0.698474006	None	None	N
Y/T	0.959	likely_pathogenic	0.9491	pathogenic	-3.319	Highly Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
Y/V	0.8486	likely_pathogenic	0.8458	pathogenic	-2.254	Highly Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	N
Y/W	0.7222	likely_pathogenic	0.7507	pathogenic	-0.553	Destabilizing	1.0	D	0.757	deleterious	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.