Submissions for variant NM_004239.4(TRIP11):c.3604A>C (p.Asn1202His)

gnomAD frequency: 0.00236  dbSNP: rs41301481

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000359112	SCV000345393	likely benign	not specified	2016-09-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000755412	SCV000389569	likely benign	Achondrogenesis, type IA	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001705435	SCV000516905	likely benign	not provided	2020-06-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000359112	SCV000605433	uncertain significance	not specified	2018-08-22	criteria provided, single submitter	clinical testing	The TRIP11 c.3604A>C, p.Asn1202His variant (rs41301481) has not been reported in the medical literature, but is listed in ClinVar (Variation ID: 290765). It is observed in the general population databases at a frequency of 0.08 percent in the 1000 Genomes Project (4/5008 alleles), 0.26 percent in the Exome Variant Server (34/13006 alleles), and 0.2 percent in the Genome Aggregation Database (565/282,578 alleles, 2 homozygotes). The asparagine at position 1202 is highly conserved (Alamut v2.11), and computational algorithms (PolyPhen-2: probably damaging; SIFT: deleterious) are deleterious on the variant's impact on TRIP11 protein structure or function. Although evidence suggests that p.Asn1202His may be a rare benign variant, there is insufficient information to determine its clinical significance with certainty.
Invitae	RCV000755412	SCV001107640	likely benign	Achondrogenesis, type IA	2024-01-29	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278324	SCV002567066	benign	Connective tissue disorder	2022-03-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002518149	SCV003710536	uncertain significance	Inborn genetic diseases	2022-11-18	criteria provided, single submitter	clinical testing	The c.3604A>C (p.N1202H) alteration is located in exon 11 (coding exon 11) of the TRIP11 gene. This alteration results from a A to C substitution at nucleotide position 3604, causing the asparagine (N) at amino acid position 1202 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001705435	SCV004130279	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	TRIP11: BS2
PreventionGenetics, part of Exact Sciences	RCV003910042	SCV004721444	likely benign	TRIP11-related condition	2022-02-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).