TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6449	19570;19571;19572	chr2:178728581;178728580;178728579	chr2:179593308;179593307;179593306
N2AB	6132	18619;18620;18621	chr2:178728581;178728580;178728579	chr2:179593308;179593307;179593306
N2A	5205	15838;15839;15840	chr2:178728581;178728580;178728579	chr2:179593308;179593307;179593306
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-48
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5717
• 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	rs1282291767	0.186	0.026	N	0.266	0.052	0.0401082797425	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs1282291767	0.186	0.026	N	0.266	0.052	0.0401082797425	gnomAD-4.0.0	1.59264E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86008E-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	0.3569	ambiguous	0.2794	benign	0.002	Stabilizing	0.919	D	0.451	neutral	None	None	None	None	N
K/C	0.8391	likely_pathogenic	0.7844	pathogenic	-0.194	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
K/D	0.6354	likely_pathogenic	0.5323	ambiguous	0.094	Stabilizing	0.976	D	0.395	neutral	None	None	None	None	N
K/E	0.205	likely_benign	0.1723	benign	0.119	Stabilizing	0.811	D	0.423	neutral	N	0.500401968	None	None	N
K/F	0.7481	likely_pathogenic	0.6558	pathogenic	-0.073	Destabilizing	0.976	D	0.522	neutral	None	None	None	None	N
K/G	0.4932	ambiguous	0.4116	ambiguous	-0.234	Destabilizing	0.919	D	0.453	neutral	None	None	None	None	N
K/H	0.4083	ambiguous	0.3379	benign	-0.487	Destabilizing	0.997	D	0.427	neutral	None	None	None	None	N
K/I	0.349	ambiguous	0.2898	benign	0.554	Stabilizing	0.952	D	0.532	neutral	None	None	None	None	N
K/L	0.2998	likely_benign	0.2263	benign	0.554	Stabilizing	0.034	N	0.333	neutral	None	None	None	None	N
K/M	0.2253	likely_benign	0.1666	benign	0.269	Stabilizing	0.968	D	0.421	neutral	N	0.46346252	None	None	N
K/N	0.4476	ambiguous	0.34	ambiguous	0.199	Stabilizing	0.968	D	0.361	neutral	N	0.458503271	None	None	N
K/P	0.4322	ambiguous	0.359	ambiguous	0.399	Stabilizing	0.988	D	0.413	neutral	None	None	None	None	N
K/Q	0.1592	likely_benign	0.1336	benign	0.049	Stabilizing	0.211	N	0.265	neutral	N	0.45445112	None	None	N
K/R	0.0978	likely_benign	0.0908	benign	-0.087	Destabilizing	0.026	N	0.266	neutral	N	0.459131349	None	None	N
K/S	0.4435	ambiguous	0.3323	benign	-0.304	Destabilizing	0.919	D	0.399	neutral	None	None	None	None	N
K/T	0.2224	likely_benign	0.1666	benign	-0.12	Destabilizing	0.896	D	0.435	neutral	N	0.50630922	None	None	N
K/V	0.3588	ambiguous	0.2897	benign	0.399	Stabilizing	0.851	D	0.439	neutral	None	None	None	None	N
K/W	0.7855	likely_pathogenic	0.7305	pathogenic	-0.071	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
K/Y	0.636	likely_pathogenic	0.5464	ambiguous	0.266	Stabilizing	0.996	D	0.493	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.