Submissions for variant NM_004793.4(LONP1):c.2203G>A (p.Val735Met)

gnomAD frequency: 0.00018  dbSNP: rs200317240

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV001332513	SCV001524861	uncertain significance	CODAS syndrome	2019-07-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001332513	SCV002053893	uncertain significance	CODAS syndrome		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001865757	SCV002116453	benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001865757	SCV002562694	uncertain significance	not provided	2023-12-28	criteria provided, single submitter	clinical testing	Identified in a patient with congenital cataracts, epiphyseal dysplasia, scoliosis, lumbar lordosis and short stature referred for genetic testing at an outside laboratory (External communication with Exeter Genomics Laboratory); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002546570	SCV003544754	uncertain significance	Inborn genetic diseases	2022-07-06	criteria provided, single submitter	clinical testing	The c.2203G>A (p.V735M) alteration is located in exon 15 (coding exon 15) of the LONP1 gene. This alteration results from a G to A substitution at nucleotide position 2203, causing the valine (V) at amino acid position 735 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004738255	SCV005342008	uncertain significance	LONP1-related disorder	2024-08-07	no assertion criteria provided	clinical testing	The LONP1 c.2203G>A variant is predicted to result in the amino acid substitution p.Val735Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.096% of alleles in individuals of African descent in gnomAD, which may be too frequent for an unreported disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.