Submissions for variant NM_001854.4(COL11A1):c.1201T>A (p.Phe401Ile)

dbSNP: rs141817156

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726651	SCV000535806	likely benign	not provided	2021-05-21	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726651	SCV000701961	uncertain significance	not provided	2017-06-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000726651	SCV001102465	likely benign	not provided	2025-01-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000726651	SCV001147359	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235214	SCV003934801	uncertain significance	not specified	2023-05-10	criteria provided, single submitter	clinical testing	Variant summary: COL11A1 c.1201T>A (p.Phe401Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00037 in 249128 control chromosomes. To our knowledge, no occurrence of c.1201T>A in individuals affected with Stickler Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Multiple laboratories reported the variant with conflicting assessments: VUS (n=2) and Likely benign (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000726651	SCV004562162	uncertain significance	not provided	2023-11-29	criteria provided, single submitter	clinical testing	The COL11A1 c.1201T>A; p.Phe401Ile variant (rs141817156), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 392525). This variant is found in the African/African-American population with an allele frequency of 0.46% (114/24762 alleles) in the Genome Aggregation Database. The phenylalanine at codon 401 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.255). Additionally, another variant at this codon (c.1201T>C; p.Phe401Leu) has been reported in a mother and daughter with Stickler syndrome (Huang 2020). The high population frequency suggests that p.Phe401Ile is unlikely associated with clinically severe presentations. However, its detection in certain effected populations does not rule out a contribution to adult onset osteoarthritis or syndromic short stature. Based on the available information, the clinical significance of the p.Phe401Ile variant is uncertain at this time. References: Huang L et al. Mutation Spectrum and De Novo Mutation Analysis in Stickler Syndrome Patients with High Myopia or Retinal Detachment. Genes (Basel). 2020 Aug 3;11(8):882. PMID: 32756486.
Ambry Genetics	RCV004975507	SCV005557906	uncertain significance	Inborn genetic diseases	2024-07-15	criteria provided, single submitter	clinical testing	The c.1201T>A (p.F401I) alteration is located in exon 8 (coding exon 8) of the COL11A1 gene. This alteration results from a T to A substitution at nucleotide position 1201, causing the phenylalanine (F) at amino acid position 401 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV000726651	SCV001924397	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000726651	SCV001969645	uncertain significance	not provided		no assertion criteria provided	clinical testing