TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23963	72112;72113;72114	chr2:178574245;178574244;178574243	chr2:179438972;179438971;179438970
N2AB	22322	67189;67190;67191	chr2:178574245;178574244;178574243	chr2:179438972;179438971;179438970
N2A	21395	64408;64409;64410	chr2:178574245;178574244;178574243	chr2:179438972;179438971;179438970
N2B	14898	44917;44918;44919	chr2:178574245;178574244;178574243	chr2:179438972;179438971;179438970
Novex-1	15023	45292;45293;45294	chr2:178574245;178574244;178574243	chr2:179438972;179438971;179438970
Novex-2	15090	45493;45494;45495	chr2:178574245;178574244;178574243	chr2:179438972;179438971;179438970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-62
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1537
• 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
K/N	rs1475718239	-2.207	0.822	N	0.688	0.286	0.216624796971	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
K/N	rs1475718239	-2.207	0.822	N	0.688	0.286	0.216624796971	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1475718239	-2.207	0.822	N	0.688	0.286	0.216624796971	gnomAD-4.0.0	6.57358E-06	None	None	None	None	N	None	2.41243E-05	0	None	0	0	None	0	0	0	0	0
K/R	None	None	0.006	N	0.291	0.096	0.208000267992	gnomAD-4.0.0	1.59279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86125E-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
K/A	0.9343	likely_pathogenic	0.9416	pathogenic	-1.499	Destabilizing	0.86	D	0.717	prob.delet.	None	None	None	None	N
K/C	0.8836	likely_pathogenic	0.8673	pathogenic	-1.457	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
K/D	0.992	likely_pathogenic	0.9929	pathogenic	-2.118	Highly Destabilizing	0.978	D	0.709	prob.delet.	None	None	None	None	N
K/E	0.8642	likely_pathogenic	0.8877	pathogenic	-1.779	Destabilizing	0.822	D	0.741	deleterious	N	0.514667639	None	None	N
K/F	0.9632	likely_pathogenic	0.9624	pathogenic	-0.726	Destabilizing	0.993	D	0.79	deleterious	None	None	None	None	N
K/G	0.9438	likely_pathogenic	0.9533	pathogenic	-2.003	Highly Destabilizing	0.86	D	0.701	prob.neutral	None	None	None	None	N
K/H	0.7182	likely_pathogenic	0.7116	pathogenic	-1.704	Destabilizing	0.978	D	0.741	deleterious	None	None	None	None	N
K/I	0.8764	likely_pathogenic	0.8863	pathogenic	-0.048	Destabilizing	0.978	D	0.787	deleterious	None	None	None	None	N
K/L	0.8186	likely_pathogenic	0.8404	pathogenic	-0.048	Destabilizing	0.86	D	0.701	prob.neutral	None	None	None	None	N
K/M	0.6115	likely_pathogenic	0.6242	pathogenic	-0.44	Destabilizing	0.997	D	0.73	prob.delet.	N	0.521559179	None	None	N
K/N	0.9584	likely_pathogenic	0.9651	pathogenic	-1.915	Destabilizing	0.822	D	0.688	prob.neutral	N	0.514667639	None	None	N
K/P	0.9984	likely_pathogenic	0.9987	pathogenic	-0.514	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
K/Q	0.4549	ambiguous	0.4709	ambiguous	-1.483	Destabilizing	0.822	D	0.718	prob.delet.	N	0.479446634	None	None	N
K/R	0.1121	likely_benign	0.1129	benign	-0.829	Destabilizing	0.006	N	0.291	neutral	N	0.443194396	None	None	N
K/S	0.9479	likely_pathogenic	0.9556	pathogenic	-2.428	Highly Destabilizing	0.86	D	0.695	prob.neutral	None	None	None	None	N
K/T	0.8386	likely_pathogenic	0.8507	pathogenic	-1.816	Destabilizing	0.822	D	0.702	prob.neutral	N	0.482622958	None	None	N
K/V	0.8372	likely_pathogenic	0.8448	pathogenic	-0.514	Destabilizing	0.978	D	0.738	prob.delet.	None	None	None	None	N
K/W	0.9487	likely_pathogenic	0.9495	pathogenic	-0.777	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
K/Y	0.8469	likely_pathogenic	0.8432	pathogenic	-0.432	Destabilizing	0.993	D	0.773	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.