TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6983	21172;21173;21174	chr2:178724428;178724427;178724426	chr2:179589155;179589154;179589153
N2AB	6666	20221;20222;20223	chr2:178724428;178724427;178724426	chr2:179589155;179589154;179589153
N2A	5739	17440;17441;17442	chr2:178724428;178724427;178724426	chr2:179589155;179589154;179589153
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-54
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1374
• 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/R	rs2078983149	None	0.896	N	0.554	0.254	0.227934060464	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
K/R	rs2078983149	None	0.896	N	0.554	0.254	0.227934060464	gnomAD-4.0.0	6.57177E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.40734E-05	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
K/A	0.9341	likely_pathogenic	0.9264	pathogenic	-1.073	Destabilizing	0.851	D	0.543	neutral	None	None	None	None	N
K/C	0.9124	likely_pathogenic	0.8894	pathogenic	-1.108	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
K/D	0.9921	likely_pathogenic	0.9914	pathogenic	-1.07	Destabilizing	0.976	D	0.659	neutral	None	None	None	None	N
K/E	0.8114	likely_pathogenic	0.826	pathogenic	-0.877	Destabilizing	0.896	D	0.515	neutral	N	0.509370812	None	None	N
K/F	0.95	likely_pathogenic	0.9502	pathogenic	-0.645	Destabilizing	0.976	D	0.797	deleterious	None	None	None	None	N
K/G	0.9723	likely_pathogenic	0.9649	pathogenic	-1.518	Destabilizing	0.976	D	0.672	neutral	None	None	None	None	N
K/H	0.6251	likely_pathogenic	0.6185	pathogenic	-1.913	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
K/I	0.8252	likely_pathogenic	0.8327	pathogenic	0.135	Stabilizing	0.952	D	0.725	prob.delet.	None	None	None	None	N
K/L	0.77	likely_pathogenic	0.7707	pathogenic	0.135	Stabilizing	0.034	N	0.415	neutral	None	None	None	None	N
K/M	0.6399	likely_pathogenic	0.6482	pathogenic	0.107	Stabilizing	0.968	D	0.705	prob.neutral	N	0.491013068	None	None	N
K/N	0.9587	likely_pathogenic	0.9549	pathogenic	-1.266	Destabilizing	0.968	D	0.549	neutral	N	0.486240128	None	None	N
K/P	0.9981	likely_pathogenic	0.9977	pathogenic	-0.24	Destabilizing	0.988	D	0.69	prob.neutral	None	None	None	None	N
K/Q	0.4664	ambiguous	0.4623	ambiguous	-1.176	Destabilizing	0.984	D	0.553	neutral	N	0.476516437	None	None	N
K/R	0.1035	likely_benign	0.1026	benign	-1.047	Destabilizing	0.896	D	0.554	neutral	N	0.421408041	None	None	N
K/S	0.9593	likely_pathogenic	0.9513	pathogenic	-1.888	Destabilizing	0.851	D	0.477	neutral	None	None	None	None	N
K/T	0.9017	likely_pathogenic	0.8933	pathogenic	-1.452	Destabilizing	0.026	N	0.333	neutral	N	0.479403273	None	None	N
K/V	0.8074	likely_pathogenic	0.8108	pathogenic	-0.24	Destabilizing	0.851	D	0.625	neutral	None	None	None	None	N
K/W	0.9426	likely_pathogenic	0.9341	pathogenic	-0.596	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/Y	0.8842	likely_pathogenic	0.8835	pathogenic	-0.258	Destabilizing	0.996	D	0.763	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.