Submissions for variant NM_017671.4(FERMT1):c.1600G>A (p.Ala534Thr) (rs2232078)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000311451	SCV000435000	benign	Kindler's syndrome	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000520612	SCV000619251	uncertain significance	not provided	2017-07-14	criteria provided, single submitter	clinical testing	The A534T variant in the FERMT1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A534T variant is observed in 174/14,502 (1.2%) alleles from individuals of South Asian background, including multiple unrelated homozygous individuals, in the ExAC dataset (Lek et al., 2016). The A534T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A534T as a variant of uncertain significance.
Invitae	RCV000520612	SCV001105653	benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000520612	SCV000986925	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 08/01/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.