TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23964	72115;72116;72117	chr2:178574242;178574241;178574240	chr2:179438969;179438968;179438967
N2AB	22323	67192;67193;67194	chr2:178574242;178574241;178574240	chr2:179438969;179438968;179438967
N2A	21396	64411;64412;64413	chr2:178574242;178574241;178574240	chr2:179438969;179438968;179438967
N2B	14899	44920;44921;44922	chr2:178574242;178574241;178574240	chr2:179438969;179438968;179438967
Novex-1	15024	45295;45296;45297	chr2:178574242;178574241;178574240	chr2:179438969;179438968;179438967
Novex-2	15091	45496;45497;45498	chr2:178574242;178574241;178574240	chr2:179438969;179438968;179438967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-62
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1765
• 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
R/K	rs770679732	-1.275	0.046	N	0.211	0.148	0.231873229951	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/K	rs770679732	-1.275	0.046	N	0.211	0.148	0.231873229951	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	2.28728E-05	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
R/A	0.8725	likely_pathogenic	0.8611	pathogenic	-2.119	Highly Destabilizing	0.953	D	0.521	neutral	None	None	None	None	N
R/C	0.3225	likely_benign	0.3306	benign	-2.048	Highly Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
R/D	0.9827	likely_pathogenic	0.9834	pathogenic	-0.845	Destabilizing	0.986	D	0.739	prob.delet.	None	None	None	None	N
R/E	0.8253	likely_pathogenic	0.8314	pathogenic	-0.644	Destabilizing	0.91	D	0.433	neutral	None	None	None	None	N
R/F	0.9355	likely_pathogenic	0.9356	pathogenic	-1.47	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
R/G	0.7854	likely_pathogenic	0.8075	pathogenic	-2.459	Highly Destabilizing	0.939	D	0.65	neutral	N	0.500908705	None	None	N
R/H	0.2786	likely_benign	0.302	benign	-2.259	Highly Destabilizing	0.998	D	0.581	neutral	None	None	None	None	N
R/I	0.8133	likely_pathogenic	0.7975	pathogenic	-1.138	Destabilizing	0.991	D	0.778	deleterious	N	0.513657362	None	None	N
R/K	0.1198	likely_benign	0.1209	benign	-1.521	Destabilizing	0.046	N	0.211	neutral	N	0.457470415	None	None	N
R/L	0.6593	likely_pathogenic	0.6339	pathogenic	-1.138	Destabilizing	0.953	D	0.65	neutral	None	None	None	None	N
R/M	0.6251	likely_pathogenic	0.6118	pathogenic	-1.552	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
R/N	0.9356	likely_pathogenic	0.9334	pathogenic	-1.312	Destabilizing	0.986	D	0.55	neutral	None	None	None	None	N
R/P	0.9959	likely_pathogenic	0.9965	pathogenic	-1.453	Destabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
R/Q	0.1893	likely_benign	0.2061	benign	-1.31	Destabilizing	0.986	D	0.534	neutral	None	None	None	None	N
R/S	0.9391	likely_pathogenic	0.9388	pathogenic	-2.333	Highly Destabilizing	0.939	D	0.615	neutral	N	0.481902169	None	None	N
R/T	0.8468	likely_pathogenic	0.8341	pathogenic	-1.918	Destabilizing	0.982	D	0.708	prob.delet.	N	0.503693408	None	None	N
R/V	0.855	likely_pathogenic	0.8397	pathogenic	-1.453	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	N
R/W	0.6322	likely_pathogenic	0.6786	pathogenic	-0.895	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
R/Y	0.8178	likely_pathogenic	0.831	pathogenic	-0.763	Destabilizing	0.998	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.