TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15723	47392;47393;47394	chr2:178618291;178618290;178618289	chr2:179483018;179483017;179483016
N2AB	14082	42469;42470;42471	chr2:178618291;178618290;178618289	chr2:179483018;179483017;179483016
N2A	13155	39688;39689;39690	chr2:178618291;178618290;178618289	chr2:179483018;179483017;179483016
N2B	6658	20197;20198;20199	chr2:178618291;178618290;178618289	chr2:179483018;179483017;179483016
Novex-1	6783	20572;20573;20574	chr2:178618291;178618290;178618289	chr2:179483018;179483017;179483016
Novex-2	6850	20773;20774;20775	chr2:178618291;178618290;178618289	chr2:179483018;179483017;179483016
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-1
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.5719
• 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	rs2057715789	None	0.997	N	0.379	0.204	0.314716216878	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs2057715789	None	0.997	N	0.379	0.204	0.314716216878	gnomAD-4.0.0	2.03042E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.4102E-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	0.5936	likely_pathogenic	0.513	ambiguous	-0.053	Destabilizing	0.998	D	0.502	neutral	None	None	None	None	N
K/C	0.8894	likely_pathogenic	0.8013	pathogenic	-0.118	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/D	0.8248	likely_pathogenic	0.7896	pathogenic	-0.013	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
K/E	0.4046	ambiguous	0.3803	ambiguous	-0.025	Destabilizing	0.997	D	0.41	neutral	N	0.394075853	None	None	N
K/F	0.9492	likely_pathogenic	0.9113	pathogenic	-0.345	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.7169	likely_pathogenic	0.6541	pathogenic	-0.237	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	N
K/H	0.5647	likely_pathogenic	0.4753	ambiguous	-0.6	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/I	0.677	likely_pathogenic	0.5927	pathogenic	0.35	Stabilizing	0.999	D	0.711	prob.delet.	N	0.483805782	None	None	N
K/L	0.6742	likely_pathogenic	0.6035	pathogenic	0.35	Stabilizing	0.998	D	0.553	neutral	None	None	None	None	N
K/M	0.5479	ambiguous	0.5046	ambiguous	0.327	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/N	0.72	likely_pathogenic	0.6679	pathogenic	0.308	Stabilizing	0.999	D	0.635	neutral	N	0.471613144	None	None	N
K/P	0.6835	likely_pathogenic	0.5636	ambiguous	0.243	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
K/Q	0.2505	likely_benign	0.223	benign	0.055	Stabilizing	0.999	D	0.623	neutral	N	0.456610089	None	None	N
K/R	0.0952	likely_benign	0.0855	benign	0.014	Stabilizing	0.997	D	0.379	neutral	N	0.460274118	None	None	N
K/S	0.7271	likely_pathogenic	0.6535	pathogenic	-0.19	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	N
K/T	0.4467	ambiguous	0.3691	ambiguous	-0.061	Destabilizing	0.999	D	0.603	neutral	N	0.460259874	None	None	N
K/V	0.5992	likely_pathogenic	0.517	ambiguous	0.243	Stabilizing	0.999	D	0.604	neutral	None	None	None	None	N
K/W	0.9256	likely_pathogenic	0.877	pathogenic	-0.329	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/Y	0.8618	likely_pathogenic	0.8034	pathogenic	0.032	Stabilizing	0.999	D	0.701	prob.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.